Variant 3-151436878-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_178822.5(IGSF10):c.7683A>G(p.Thr2561Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 1,613,988 control chromosomes in the GnomAD database, including 563,505 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 53896 hom., cov: 31)

Exomes 𝑓: 0.83 ( 509609 hom. )

Consequence

IGSF10
NM_178822.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.78

Variant links:

Genes affected

IGSF10 (HGNC:26384): (immunoglobulin superfamily member 10) Predicted to be involved in regulation of neuron migration. Predicted to act upstream of or within ossification. Located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

IGSF10 links:

MED12L (HGNC:16050): (mediator complex subunit 12L) The protein encoded by this gene is part of the Mediator complex, which is involved in transcriptional coactivation of nearly all RNA polymerase II-dependent genes. The Mediator complex links gene-specific transcriptional activators with the basal transcription machinery. [provided by RefSeq, May 2010]

MED12L links:

IGSF10 (HGNC:):

IGSF10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 3-151436878-T-C is Benign according to our data. Variant chr3-151436878-T-C is described in ClinVar as [Benign]. Clinvar id is 1598558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.78 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF10	NM_178822.5 linkuse as main transcript	c.7683A>G	p.Thr2561Thr	synonymous_variant	8/8	ENST00000282466.4	NP_849144.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF10	ENST00000282466.4 linkuse as main transcript	c.7683A>G	p.Thr2561Thr	synonymous_variant	8/8	1	NM_178822.5	ENSP00000282466.3		Q6WRI0-1

Frequencies

GnomAD3 genomes

AF:

0.840

AC:

127745

AN:

152062

Hom.:

53861

Cov.:

show subpopulations

Gnomad AFR

AF:

0.850

Gnomad AMI

AF:

0.793

Gnomad AMR

AF:

0.817

Gnomad ASJ

AF:

0.930

Gnomad EAS

AF:

0.891

Gnomad SAS

AF:

0.812

Gnomad FIN

AF:

0.774

Gnomad MID

AF:

0.965

Gnomad NFE

AF:

0.843

Gnomad OTH

AF:

0.864

GnomAD3 exomes

AF:

0.829

AC:

208214

AN:

251302

Hom.:

86683

AF XY:

0.833

AC XY:

113079

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.844

Gnomad AMR exome

AF:

0.745

Gnomad ASJ exome

AF:

0.918

Gnomad EAS exome

AF:

0.905

Gnomad SAS exome

AF:

0.817

Gnomad FIN exome

AF:

0.780

Gnomad NFE exome

AF:

0.843

Gnomad OTH exome

AF:

0.839

GnomAD4 exome

AF:

0.834

AC:

1219503

AN:

1461808

Hom.:

509609

Cov.:

AF XY:

0.835

AC XY:

607028

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.852

Gnomad4 AMR exome

AF:

0.754

Gnomad4 ASJ exome

AF:

0.914

Gnomad4 EAS exome

AF:

0.843

Gnomad4 SAS exome

AF:

0.817

Gnomad4 FIN exome

AF:

0.782

Gnomad4 NFE exome

AF:

0.837

Gnomad4 OTH exome

AF:

0.849

GnomAD4 genome

AF:

0.840

AC:

127840

AN:

152180

Hom.:

53896

Cov.:

AF XY:

0.835

AC XY:

62146

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.850

Gnomad4 AMR

AF:

0.817

Gnomad4 ASJ

AF:

0.930

Gnomad4 EAS

AF:

0.891

Gnomad4 SAS

AF:

0.811

Gnomad4 FIN

AF:

0.774

Gnomad4 NFE

AF:

0.843

Gnomad4 OTH

AF:

0.865

Alfa

AF:

0.848

Hom.:

100231

Bravo

AF:

0.843

Asia WGS

AF:

0.854

AC:

2969

AN:

3478

EpiCase

AF:

0.858

EpiControl

AF:

0.861

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

IGSF10-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.028

DANN

Benign

0.57

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