rs1135791

Positions:

chr2-230177560-A-G

Variant summary

Our verdict is Benign. Variant got -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. 15/20 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:5

Conservation

PhyloP100: -0.542

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 334902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-230177560-A-G is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SP110	NM_080424.4 linkuse as main transcript	c.1568T>C	p.Met523Thr	missense_variant	14/19	ENST00000258381.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SP110	ENST00000258381.11 linkuse as main transcript	c.1568T>C	p.Met523Thr	missense_variant	14/19	2	NM_080424.4	P1	Q9HB58-6

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

GnomAD3 exomes

AF:

0.419

AC:

105350

AN:

251440

Hom.:

23957

AF XY:

0.430

AC XY:

58431

AN XY:

135888

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 SAS exome

AF:

0.427

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

Gnomad4 AFR exome

AF:

0.235

Gnomad4 AMR exome

AF:

0.302

Gnomad4 ASJ exome

AF:

0.518

Gnomad4 EAS exome

AF:

0.169

Gnomad4 SAS exome

AF:

0.420

Gnomad4 FIN exome

AF:

0.411

Gnomad4 NFE exome

AF:

0.509

Gnomad4 OTH exome

AF:

0.454

GnomAD4 genome

AF:

0.399

AC:

60710

AN:

152112

Hom.:

13277

Cov.:

AF XY:

0.392

AC XY:

29179

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.243

Gnomad4 AMR

AF:

0.373

Gnomad4 ASJ

AF:

0.518

Gnomad4 EAS

AF:

0.170

Gnomad4 SAS

AF:

0.420

Gnomad4 FIN

AF:

0.402

Gnomad4 NFE

AF:

0.506

Gnomad4 OTH

AF:

0.419

Alfa

AF:

0.481

Hom.:

31105

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hepatic veno-occlusive disease-immunodeficiency syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.36

DANN

Benign

0.28

DEOGEN2

Benign

0.086

.;T;T;.;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.0044

T;T;T;T;T

MetaRNN

Benign

0.000025

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.85

N;N;.;N;.

MutationTaster

Benign

1.0

P;P;P;P;P;P

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.59

N;N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.28

T;T;T;T;T

Sift4G

Benign

0.24

T;T;T;T;T

Polyphen

0.0

B;B;B;.;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over