Variant chr3-118904700-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001015887.3(IGSF11):c.802T>C(p.Trp268Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000856 in 1,612,534 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00088 ( 2 hom. )

Consequence

IGSF11
NM_001015887.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.63

Variant links:

Genes affected

IGSF11 (HGNC:16669): (immunoglobulin superfamily member 11) IGSF11 is an immunoglobulin (Ig) superfamily member that is preferentially expressed in brain and testis. It shares significant homology with coxsackievirus and adenovirus receptor (CXADR; MIM 602621) and endothelial cell-selective adhesion molecule (ESAM).[supplied by OMIM, Apr 2005]

IGSF11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF11	NM_001015887.3 linkuse as main transcript	c.802T>C	p.Trp268Arg	missense_variant	6/7	ENST00000393775.7	NP_001015887.1	Q5DX21-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF11	ENST00000393775.7 linkuse as main transcript	c.802T>C	p.Trp268Arg	missense_variant	6/7	1	NM_001015887.3	ENSP00000377370.2		Q5DX21-1

Frequencies

GnomAD3 genomes

AF:

0.000637

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00123

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000443

AC:

111

AN:

250632

Hom.:

AF XY:

0.000391

AC XY:

AN XY:

135628

show subpopulations

Gnomad AFR exome

AF:

0.0000625

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000899

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000879

AC:

1284

AN:

1460374

Hom.:

Cov.:

AF XY:

0.000809

AC XY:

588

AN XY:

726558

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00113

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000637

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.000565

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00123

Gnomad4 OTH

AF:

0.000958

Alfa

AF:

0.000879

Hom.:

Bravo

AF:

0.000499

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000511

AC:

EpiCase

AF:

0.000710

EpiControl

AF:

0.000415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2021

The c.802T>C (p.W268R) alteration is located in exon 6 (coding exon 6) of the IGSF11 gene. This alteration results from a T to C substitution at nucleotide position 802, causing the tryptophan (W) at amino acid position 268 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Pathogenic

0.35

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

.;T;.;.;.;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.70

.;T;T;T;T;T

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.66

D;D;D;D;D;D

MetaSVM

Uncertain

-0.049

MutationAssessor

Benign

1.6

.;L;.;.;.;.

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.7

N;N;N;N;N;D

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0020

D;D;D;D;D;D

Sift4G

Uncertain

0.026

D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;D;D

Vest4

0.93

MutPred

0.52

.;Gain of sheet (P = 0.0149);.;.;.;.;

MVP

0.79

MPC

1.4

ClinPred

0.23

GERP RS

5.3

Varity_R

0.57

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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