Variant 1-160491181-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001184714.2(SLAMF6):c.590C>T(p.Ala197Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLAMF6
NM_001184714.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

Variant links:

Genes affected

SLAMF6 (HGNC:21392): (SLAM family member 6) The protein encoded by this gene is a type I transmembrane protein, belonging to the CD2 subfamily of the immunoglobulin superfamily. This encoded protein is expressed on Natural killer (NK), T, and B lymphocytes. It undergoes tyrosine phosphorylation and associates with the Src homology 2 domain-containing protein (SH2D1A) as well as with SH2 domain-containing phosphatases (SHPs). It functions as a coreceptor in the process of NK cell activation. It can also mediate inhibitory signals in NK cells from X-linked lymphoproliferative patients. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, May 2010]

SLAMF6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLAMF6	NM_001184714.2 linkuse as main transcript	c.590C>T	p.Ala197Val	missense_variant	3/8	ENST00000368057.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLAMF6	ENST00000368057.8 linkuse as main transcript	c.590C>T	p.Ala197Val	missense_variant	3/8	1	NM_001184714.2	A2	Q96DU3-1
SLAMF6	ENST00000368059.7 linkuse as main transcript	c.590C>T	p.Ala197Val	missense_variant	3/8	1		P4	Q96DU3-2
SLAMF6	ENST00000368055.1 linkuse as main transcript	c.257C>T	p.Ala86Val	missense_variant	2/7	2			Q96DU3-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461790

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 27, 2023

The c.590C>T (p.A197V) alteration is located in exon 3 (coding exon 3) of the SLAMF6 gene. This alteration results from a C to T substitution at nucleotide position 590, causing the alanine (A) at amino acid position 197 to be replaced by a valine (V). 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

0.31

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.65

.;D;.

Eigen

Benign

0.054

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.83

T;T;T

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.71

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Benign

0.21

Sift

Benign

0.070

T;D;D

Sift4G

Benign

0.083

T;T;D

Polyphen

1.0

D;D;.

Vest4

0.72

MutPred

0.76

Gain of catalytic residue at A197 (P = 0.0945);Gain of catalytic residue at A197 (P = 0.0945);.;

MVP

0.33

MPC

0.89

ClinPred

0.96

GERP RS

3.5

Varity_R

0.67

gMVP

0.87

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over