chr2-230172144-C-T

Position:

chr2-230172144-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_080424.4(SP110):c.1737G>A(p.Met579Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0674 in 1,611,874 control chromosomes in the GnomAD database, including 4,258 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 301 hom., cov: 33)

Exomes 𝑓: 0.069 ( 3957 hom. )

Consequence

SP110
NM_080424.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.229

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:

ENSG00000225963 (HGNC:):

ENSG00000225963 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=0.0022109747).

BP6

Variant 2-230172144-C-T is Benign according to our data. Variant chr2-230172144-C-T is described in ClinVar as [Benign]. Clinvar id is 334897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.078 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP110	NM_080424.4 linkuse as main transcript	c.1737G>A	p.Met579Ile	missense_variant	16/19	ENST00000258381.11	NP_536349.3	Q9HB58-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11 linkuse as main transcript	c.1737G>A	p.Met579Ile	missense_variant	16/19	2	NM_080424.4	ENSP00000258381.6		Q9HB58-6

Frequencies

GnomAD3 genomes

AF:

0.0531

AC:

8089

AN:

152208

Hom.:

301

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.0521

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.0538

Gnomad FIN

AF:

0.0339

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0797

Gnomad OTH

AF:

0.0632

GnomAD3 exomes

AF:

0.0599

AC:

15056

AN:

251380

Hom.:

594

AF XY:

0.0620

AC XY:

8423

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.0127

Gnomad AMR exome

AF:

0.0357

Gnomad ASJ exome

AF:

0.146

Gnomad EAS exome

AF:

0.00299

Gnomad SAS exome

AF:

0.0541

Gnomad FIN exome

AF:

0.0315

Gnomad NFE exome

AF:

0.0818

Gnomad OTH exome

AF:

0.0740

GnomAD4 exome

AF:

0.0689

AC:

100601

AN:

1459548

Hom.:

3957

Cov.:

AF XY:

0.0690

AC XY:

50146

AN XY:

726272

show subpopulations

Gnomad4 AFR exome

AF:

0.0125

Gnomad4 AMR exome

AF:

0.0383

Gnomad4 ASJ exome

AF:

0.145

Gnomad4 EAS exome

AF:

0.00159

Gnomad4 SAS exome

AF:

0.0525

Gnomad4 FIN exome

AF:

0.0330

Gnomad4 NFE exome

AF:

0.0755

Gnomad4 OTH exome

AF:

0.0671

GnomAD4 genome

AF:

0.0531

AC:

8082

AN:

152326

Hom.:

301

Cov.:

AF XY:

0.0508

AC XY:

3783

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0131

Gnomad4 AMR

AF:

0.0520

Gnomad4 ASJ

AF:

0.136

Gnomad4 EAS

AF:

0.00232

Gnomad4 SAS

AF:

0.0528

Gnomad4 FIN

AF:

0.0339

Gnomad4 NFE

AF:

0.0797

Gnomad4 OTH

AF:

0.0625

Alfa

AF:

0.0758

Hom.:

1105

Bravo

AF:

0.0522

TwinsUK

AF:

0.0709

AC:

263

ALSPAC

AF:

0.0721

AC:

278

ESP6500AA

AF:

0.0168

AC:

ESP6500EA

AF:

0.0826

AC:

710

ExAC

AF:

0.0606

AC:

7353

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.0806

EpiControl

AF:

0.0835

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hepatic veno-occlusive disease-immunodeficiency syndrome

Benign:2

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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

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: MAF -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.43

CADD

Benign

8.1

DANN

Benign

0.64

DEOGEN2

Benign

0.0048

.;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.82

T;T

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.84

L;L

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.96

N;N

REVEL

Benign

0.16

Sift

Benign

0.48

T;T

Sift4G

Benign

0.43

T;T

Polyphen

0.046

B;B

Vest4

0.094

MutPred

0.77

Gain of methylation at K580 (P = 0.0439);Gain of methylation at K580 (P = 0.0439);

MPC

0.16

ClinPred

0.00030

GERP RS

2.7

Varity_R

0.065

gMVP

0.14

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