2-230177560-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_080424.4(SP110):c.1568T>C(p.Met523Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,612,900 control chromosomes in the GnomAD database, including 183,714 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 13277 hom., cov: 32)

Exomes 𝑓: 0.48 ( 170437 hom. )

Consequence

SP110
NM_080424.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.542

Publications

50 publications found

Variant links:

Genes affected

SP110 (HGNC:5401): (SP110 nuclear body protein) The nuclear body is a multiprotein complex that may have a role in the regulation of gene transcription. This gene is a member of the SP100/SP140 family of nuclear body proteins and encodes a leukocyte-specific nuclear body component. The protein can function as an activator of gene transcription and may serve as a nuclear hormone receptor coactivator. In addition, it has been suggested that the protein may play a role in ribosome biogenesis and in the induction of myeloid cell differentiation. Alternative splicing has been observed for this gene and three transcript variants, encoding distinct isoforms, have been identified. [provided by RefSeq, Jul 2008]

SP110 Gene-Disease associations (from GenCC):

hepatic veno-occlusive disease-immunodeficiency syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Ambry Genetics

SP110 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.4625439E-5).

BP6

Variant 2-230177560-A-G is Benign according to our data. Variant chr2-230177560-A-G is described in ClinVar as Benign. ClinVar VariationId is 334902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080424.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SP110	NM_080424.4	MANE Select	c.1568T>C	p.Met523Thr	missense	Exon 14 of 19	NP_536349.3
SP110	NM_001378442.1		c.1586T>C	p.Met529Thr	missense	Exon 15 of 20	NP_001365371.1
SP110	NM_001378443.1		c.1568T>C	p.Met523Thr	missense	Exon 14 of 19	NP_001365372.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SP110	ENST00000258381.11	TSL:2 MANE Select	c.1568T>C	p.Met523Thr	missense	Exon 14 of 19	ENSP00000258381.6
SP110	ENST00000358662.9	TSL:1	c.1568T>C	p.Met523Thr	missense	Exon 14 of 18	ENSP00000351488.4
SP110	ENST00000258382.10	TSL:1	c.1568T>C	p.Met523Thr	missense	Exon 14 of 15	ENSP00000258382.5

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60683

AN:

151992

Hom.:

13273

Cov.:

show subpopulations

Gnomad AFR

AF:

0.243

Gnomad AMI

AF:

0.565

Gnomad AMR

AF:

0.374

Gnomad ASJ

AF:

0.518

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.402

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.506

Gnomad OTH

AF:

0.417

GnomAD2 exomes

AF:

0.419

AC:

105350

AN:

251440

AF XY:

0.430

show subpopulations

Gnomad AFR exome

AF:

0.236

Gnomad AMR exome

AF:

0.292

Gnomad ASJ exome

AF:

0.523

Gnomad EAS exome

AF:

0.154

Gnomad FIN exome

AF:

0.411

Gnomad NFE exome

AF:

0.515

Gnomad OTH exome

AF:

0.443

GnomAD4 exome

AF:

0.476

AC:

695138

AN:

1460788

Hom.:

170437

Cov.:

AF XY:

0.476

AC XY:

345962

AN XY:

726768

show subpopulations

African (AFR)

AF:

0.235

AC:

7867

AN:

33470

American (AMR)

AF:

0.302

AC:

13506

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

13528

AN:

26130

East Asian (EAS)

AF:

0.169

AC:

6701

AN:

39668

South Asian (SAS)

AF:

0.420

AC:

36262

AN:

86244

European-Finnish (FIN)

AF:

0.411

AC:

21941

AN:

53410

Middle Eastern (MID)

AF:

0.500

AC:

2886

AN:

5768

European-Non Finnish (NFE)

AF:

0.509

AC:

565036

AN:

1111012

Other (OTH)

AF:

0.454

AC:

27411

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

20246

40492

60739

80985

101231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16090

32180

48270

64360

80450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.399

AC:

60710

AN:

152112

Hom.:

13277

Cov.:

AF XY:

0.392

AC XY:

29179

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.243

AC:

10087

AN:

41522

American (AMR)

AF:

0.373

AC:

5709

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

1797

AN:

3468

East Asian (EAS)

AF:

0.170

AC:

876

AN:

5160

South Asian (SAS)

AF:

0.420

AC:

2028

AN:

4824

European-Finnish (FIN)

AF:

0.402

AC:

4248

AN:

10572

Middle Eastern (MID)

AF:

0.490

AC:

143

AN:

292

European-Non Finnish (NFE)

AF:

0.506

AC:

34425

AN:

67968

Other (OTH)

AF:

0.419

AC:

884

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1811

3623

5434

7246

9057

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

578

1156

1734

2312

2890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.471

Hom.:

39227

Bravo

AF:

0.389

TwinsUK

AF:

0.513

AC:

1903

ALSPAC

AF:

0.499

AC:

1924

ESP6500AA

AF:

0.255

AC:

1124

ESP6500EA

AF:

0.501

AC:

4306

ExAC

AF:

0.426

AC:

51677

Asia WGS

AF:

0.279

AC:

973

AN:

3478

EpiCase

AF:

0.510

EpiControl

AF:

0.516

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hepatic veno-occlusive disease-immunodeficiency syndrome

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 64% of patients studied by a panel of primary immunodeficiencies. Number of patients: 61. Only high quality variants are reported.

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.36

(source)

DANN

Benign

0.28

DEOGEN2

Benign

0.086

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.0044

MetaRNN

Benign

0.000025

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.85

PhyloP100

-0.54

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.59

REVEL

Benign

0.15

Sift

Benign

0.28

Sift4G

Benign

0.24

Polyphen

0.0

Vest4

0.040

MPC

0.15

ClinPred

0.017

GERP RS

-0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.033

gMVP

0.51

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over