Variant 1-160753125-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021181.5(SLAMF7):c.956T>G(p.Leu319Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,574 control chromosomes in the GnomAD database, including 1 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

SLAMF7
NM_021181.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.503

Variant links:

Genes affected

SLAMF7 (HGNC:21394): (SLAM family member 7) Enables identical protein binding activity. Predicted to be involved in adaptive immune response. Predicted to act upstream of or within regulation of natural killer cell activation. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

SLAMF7 links:

SLAMF7 (HGNC:):

SLAMF7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.004416853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLAMF7	NM_021181.5 linkuse as main transcript	c.956T>G	p.Leu319Arg	missense_variant	7/7	ENST00000368043.8	NP_067004.3	Q9NQ25-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLAMF7	ENST00000368043.8 linkuse as main transcript	c.956T>G	p.Leu319Arg	missense_variant	7/7	1	NM_021181.5	ENSP00000357022.3		Q9NQ25-1

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000482

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250928

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135640

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00000882

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461546

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000250

AC:

AN:

152028

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000482

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.000378

ExAC

AF:

0.00000824

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

Oct 13, 2023

The c.956T>G (p.L319R) alteration is located in exon 7 (coding exon 7) of the SLAMF7 gene. This alteration results from a T to G substitution at nucleotide position 956, causing the leucine (L) at amino acid position 319 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

Benign

0.080

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.18

.;.;.;T;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.71

T;T;T;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.0044

T;T;T;T;T

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.87

N;N;.;N;N

REVEL

Benign

0.048

Sift

Benign

0.76

T;D;.;T;T

Sift4G

Uncertain

0.012

D;D;D;D;D

Polyphen

1.0, 1.0

.;.;D;D;D

Vest4

0.23

MutPred

0.28

.;.;.;Gain of disorder (P = 0.0245);.;

MVP

0.60

MPC

0.72

ClinPred

0.48

GERP RS

-2.2

Varity_R

0.076

gMVP

0.43

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