3-151436721-C-T

Position:

chr3-151436721-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_178822.5(IGSF10):c.7840G>A(p.Asp2614Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00612 in 1,612,408 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 72 hom. )

Consequence

IGSF10
NM_178822.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.52

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0074222684).

BP6

Variant 3-151436721-C-T is Benign according to our data. Variant chr3-151436721-C-T is described in ClinVar as [Benign]. Clinvar id is 708312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00419 (638/152306) while in subpopulation SAS AF= 0.0239 (115/4820). AF 95% confidence interval is 0.0203. There are 3 homozygotes in gnomad4. There are 319 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF10	NM_178822.5 linkuse as main transcript	c.7840G>A	p.Asp2614Asn	missense_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.7840G>A	p.Asp2614Asn	missense_variant	8/8	1	NM_178822.5	ENSP00000282466.3		Q6WRI0-1

Frequencies

GnomAD3 genomes

AF:

0.00419

AC:

637

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0238

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00586

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00697

AC:

1740

AN:

249572

Hom.:

AF XY:

0.00817

AC XY:

1102

AN XY:

134828

show subpopulations

Gnomad AFR exome

AF:

0.000985

Gnomad AMR exome

AF:

0.00181

Gnomad ASJ exome

AF:

0.00989

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0243

Gnomad FIN exome

AF:

0.00144

Gnomad NFE exome

AF:

0.00678

Gnomad OTH exome

AF:

0.00509

GnomAD4 exome

AF:

0.00632

AC:

9234

AN:

1460102

Hom.:

Cov.:

AF XY:

0.00710

AC XY:

5157

AN XY:

726290

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00184

Gnomad4 ASJ exome

AF:

0.00967

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0249

Gnomad4 FIN exome

AF:

0.00178

Gnomad4 NFE exome

AF:

0.00554

Gnomad4 OTH exome

AF:

0.00653

GnomAD4 genome

AF:

0.00419

AC:

638

AN:

152306

Hom.:

Cov.:

AF XY:

0.00428

AC XY:

319

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0239

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00587

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00595

Hom.:

Bravo

AF:

0.00344

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00686

AC:

ExAC

AF:

0.00799

AC:

970

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.00758

EpiControl

AF:

0.00652

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2022	IGSF10: PP2, BP4, BS1, BS2; MED12L: BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 25, 2023	- -

IGSF10-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 14, 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

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0074

MetaSVM

Benign

-0.34

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.42

Sift

Uncertain

0.0080

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.47

MVP

0.85

MPC

0.18

ClinPred

0.014

GERP RS

5.3

Varity_R

0.75

gMVP

0.60

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