Variant X-66027491-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_007268.3(VSIG4):c.793A>T(p.Thr265Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000691 in 1,203,040 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 320 hemizygotes in GnomAD. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T265I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., 10 hem., cov: 23)

Exomes 𝑓: 0.00073 ( 0 hom. 310 hem. )

Consequence

VSIG4
NM_007268.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.223

Variant links:

Genes affected

VSIG4 (HGNC:17032): (V-set and immunoglobulin domain containing 4) This gene encodes a v-set and immunoglobulin-domain containing protein that is structurally related to the B7 family of immune regulatory proteins. The encoded protein may be a negative regulator of T-cell responses. This protein is also a receptor for the complement component 3 fragments C3b and iC3b. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

VSIG4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005371928).

BS2

High Hemizygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VSIG4	NM_007268.3 linkuse as main transcript	c.793A>T	p.Thr265Ser	missense_variant	5/8	ENST00000374737.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VSIG4	ENST00000374737.9 linkuse as main transcript	c.793A>T	p.Thr265Ser	missense_variant	5/8	1	NM_007268.3	P2	Q9Y279-1

Frequencies

GnomAD3 genomes

AF:

0.000338

AC:

AN:

112472

Hom.:

Cov.:

AF XY:

0.000289

AC XY:

AN XY:

34650

show subpopulations

Gnomad AFR

AF:

0.0000647

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000939

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00182

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.000526

Gnomad OTH

AF:

0.000661

GnomAD3 exomes

AF:

0.000580

AC:

AN:

167357

Hom.:

AF XY:

0.000894

AC XY:

AN XY:

54817

show subpopulations

Gnomad AFR exome

AF:

0.000165

Gnomad AMR exome

AF:

0.000153

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00292

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000561

Gnomad OTH exome

AF:

0.000240

GnomAD4 exome

AF:

0.000727

AC:

793

AN:

1090514

Hom.:

Cov.:

AF XY:

0.000868

AC XY:

310

AN XY:

357298

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.000173

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00274

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000742

Gnomad4 OTH exome

AF:

0.000306

GnomAD4 genome

AF:

0.000338

AC:

AN:

112526

Hom.:

Cov.:

AF XY:

0.000288

AC XY:

AN XY:

34714

show subpopulations

Gnomad4 AFR

AF:

0.0000645

Gnomad4 AMR

AF:

0.0000938

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00182

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000526

Gnomad4 OTH

AF:

0.000652

Alfa

AF:

0.000452

Hom.:

Bravo

AF:

0.000276

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00138

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.000455

AC:

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

Sep 02, 2021

The c.793A>T (p.T265S) alteration is located in exon 5 (coding exon 5) of the VSIG4 gene. This alteration results from a A to T substitution at nucleotide position 793, causing the threonine (T) at amino acid position 265 to be replaced by a serine (S). 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

Benign

0.093

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.63

CADD

Benign

2.7

DANN

Benign

0.73

DEOGEN2

Benign

0.12

T;.;.

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.0054

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.49

N;N;N

REVEL

Benign

0.016

Sift

Pathogenic

0.0

D;D;D

Sift4G

Benign

0.20

T;T;T

Polyphen

0.82

P;P;B

Vest4

0.15

MutPred

0.25

Gain of disorder (P = 0.0788);Gain of disorder (P = 0.0788);.;

MVP

0.095

MPC

0.0051

ClinPred

0.051

GERP RS

1.4

Varity_R

0.11

gMVP

0.28

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