1-160490650-G-T

Variant names:

• chr1-160490650-G-T
• NM_001184714.2:c.682C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001184714.2(SLAMF6):​c.682C>A​(p.Leu228Met) 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 benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLAMF6 NM_001184714.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.291

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 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=0.060269028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLAMF6	NM_001184714.2	c.682C>A	p.Leu228Met	missense_variant	Exon 4 of 8	ENST00000368057.8	NP_001171643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLAMF6	ENST00000368057.8	c.682C>A	p.Leu228Met	missense_variant	Exon 4 of 8	1	NM_001184714.2	ENSP00000357036.3
SLAMF6	ENST00000368059.7	c.682C>A	p.Leu228Met	missense_variant	Exon 4 of 8	1		ENSP00000357038.3
SLAMF6	ENST00000368055.1	c.349C>A	p.Leu117Met	missense_variant	Exon 3 of 7	2		ENSP00000357034.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.682C>A (p.L228M) alteration is located in exon 4 (coding exon 4) of the SLAMF6 gene. This alteration results from a C to A substitution at nucleotide position 682, causing the leucine (L) at amino acid position 228 to be replaced by a methionine (M). 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	0.12
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.052
DANN	Benign	0.31
DEOGEN2	Benign	0.24	.;T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00032	N
LIST_S2	Benign	0.35	T;T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.060	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;L;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.40	N;N;N
REVEL	Benign	0.050
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.086	T;T;T
Polyphen		0.41	.;B;.
Vest4		0.090
MutPred		0.41		Loss of catalytic residue at L228 (P = 0.0013);Loss of catalytic residue at L228 (P = 0.0013);.;
MVP		0.15
MPC		0.25
ClinPred		0.10	T
GERP RS		-6.4
Varity_R		0.062
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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.

Other links and lift over

hg19: chr1-160460440;