1-160490650-G-C

Variant names:

• chr1-160490650-G-C
• rs1653235869
• NM_001184714.2:c.682C>G

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.682C>G​(p.Leu228Val) 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. L228M) 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: -0.291
• 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=0.038324624).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001184714.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLAMF6	NM_001184714.2	MANE Select	c.682C>G	p.Leu228Val	missense	Exon 4 of 8	NP_001171643.1	Q96DU3-1
	SLAMF6	NM_052931.5		c.682C>G	p.Leu228Val	missense	Exon 4 of 8	NP_443163.1	Q96DU3-2
	SLAMF6	NM_001184715.2		c.535C>G	p.Leu179Val	missense	Exon 4 of 8	NP_001171644.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLAMF6	ENST00000368057.8	TSL:1 MANE Select	c.682C>G	p.Leu228Val	missense	Exon 4 of 8	ENSP00000357036.3	Q96DU3-1
	SLAMF6	ENST00000368059.7	TSL:1	c.682C>G	p.Leu228Val	missense	Exon 4 of 8	ENSP00000357038.3	Q96DU3-2
	SLAMF6	ENST00000873202.1		c.535C>G	p.Leu179Val	missense	Exon 4 of 8	ENSP00000543261.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.012
DANN	Benign	0.11
DEOGEN2	Benign	0.14	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0076	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.29
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.019
Sift	Benign	0.71	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.018
MutPred		0.39		Loss of stability (P = 0.1698)
MVP		0.11
MPC		0.25
ClinPred		0.037	T
GERP RS		-6.4
Varity_R		0.028
gMVP		0.25
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
SpliceAI score (max)		0.060		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: rs1653235869; hg19: chr1-160460440;