1-160496166-A-C

Position:

• chr1-160496166-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001184714.2(SLAMF6):​c.277T>G​(p.Ser93Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLAMF6 NM_001184714.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.767

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLAMF6	NM_001184714.2	c.277T>G	p.Ser93Ala	missense_variant	2/8	ENST00000368057.8	NP_001171643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLAMF6	ENST00000368057.8	c.277T>G	p.Ser93Ala	missense_variant	2/8	1	NM_001184714.2	ENSP00000357036.3
SLAMF6	ENST00000368059.7	c.277T>G	p.Ser93Ala	missense_variant	2/8	1		ENSP00000357038.3
SLAMF6	ENST00000368055.1	c.50-4778T>G		intron_variant		2		ENSP00000357034.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 14, 2024

The c.277T>G (p.S93A) alteration is located in exon 2 (coding exon 2) of the SLAMF6 gene. This alteration results from a T to G substitution at nucleotide position 277, causing the serine (S) at amino acid position 93 to be replaced by an alanine (A). 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	0.17
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.62	.;D
Eigen	Uncertain	0.19
Eigen_PC	Benign	-0.00095
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.014	T
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Pathogenic	2.9	M;M
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Benign	0.27
Sift	Uncertain	0.024	D;D
Sift4G	Uncertain	0.029	D;D
Polyphen		1.0	D;D
Vest4		0.42
MutPred		0.82		Loss of disorder (P = 0.0318);Loss of disorder (P = 0.0318);
MVP		0.60
MPC		0.81
ClinPred		0.90	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.32
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

Other links and lift over

dbSNP: rs1653565902; hg19: chr1-160465956;