chr1-160490647-A-T

Variant names:

• chr1-160490647-A-T
• rs1653235544
• NM_001184714.2:c.685T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001184714.2(SLAMF6):​c.685T>A​(p.Phe229Ile) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F229L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLAMF6 NM_001184714.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040993035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLAMF6	NM_001184714.2	c.685T>A	p.Phe229Ile	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.685T>A	p.Phe229Ile	missense_variant	Exon 4 of 8	1	NM_001184714.2	ENSP00000357036.3
SLAMF6	ENST00000368059.7	c.685T>A	p.Phe229Ile	missense_variant	Exon 4 of 8	1		ENSP00000357038.3
SLAMF6	ENST00000368055.1	c.352T>A	p.Phe118Ile	missense_variant	Exon 3 of 7	2		ENSP00000357034.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.0030
DANN	Benign	0.31
DEOGEN2	Benign	0.096	.;T;.
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.00046	N
LIST_S2	Benign	0.26	T;T;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.041	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N;N;.
PhyloP100		-1.3
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.73	N;N;N
REVEL	Benign	0.0070
Sift	Benign	0.66	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.074
MutPred		0.41		Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);.;
MVP		0.061
MPC		0.34
ClinPred		0.024	T
GERP RS		-8.6
Varity_R		0.019
gMVP		0.23
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs1653235544; hg19: chr1-160460437;