chr1-160490647-A-G

Position:

• chr1-160490647-A-G

Variant summary

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

The NM_001184714.2(SLAMF6):​c.685T>C​(p.Phe229Leu) 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: -1.27

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=0.036347628).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLAMF6	NM_001184714.2	c.685T>C	p.Phe229Leu	missense_variant	4/8	ENST00000368057.8	NP_001171643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLAMF6	ENST00000368057.8	c.685T>C	p.Phe229Leu	missense_variant	4/8	1	NM_001184714.2	ENSP00000357036.3
SLAMF6	ENST00000368059.7	c.685T>C	p.Phe229Leu	missense_variant	4/8	1		ENSP00000357038.3
SLAMF6	ENST00000368055.1	c.352T>C	p.Phe118Leu	missense_variant	3/7	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2024

The c.685T>C (p.F229L) alteration is located in exon 4 (coding exon 4) of the SLAMF6 gene. This alteration results from a T to C substitution at nucleotide position 685, causing the phenylalanine (F) at amino acid position 229 to be replaced by a leucine (L). 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	0.28
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.018
DANN	Benign	0.26
DEOGEN2	Benign	0.084	.;T;.
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.0052	N
LIST_S2	Benign	0.33	T;T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.036	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.62	N;N;N
REVEL	Benign	0.0060
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.86	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.010
MutPred		0.41		Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);.;
MVP		0.055
MPC		0.29
ClinPred		0.022	T
GERP RS		-8.6
Varity_R		0.019
gMVP		0.23

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.

Other links and lift over

hg19: chr1-160460437;