GeneBe

rs1653235869

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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. 16/22 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

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.291

Publications

0 publications found
Variant links:
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]

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ACMG classification

Classification was made for transcript

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=0.060269028).

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.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
SLAMF6
NM_001184714.2
MANE Select
c.682C>Ap.Leu228Met
missense
Exon 4 of 8NP_001171643.1Q96DU3-1
SLAMF6
NM_052931.5
c.682C>Ap.Leu228Met
missense
Exon 4 of 8NP_443163.1Q96DU3-2
SLAMF6
NM_001184715.2
c.535C>Ap.Leu179Met
missense
Exon 4 of 8NP_001171644.1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
SLAMF6
ENST00000368057.8
TSL:1 MANE Select
c.682C>Ap.Leu228Met
missense
Exon 4 of 8ENSP00000357036.3Q96DU3-1
SLAMF6
ENST00000368059.7
TSL:1
c.682C>Ap.Leu228Met
missense
Exon 4 of 8ENSP00000357038.3Q96DU3-2
SLAMF6
ENST00000873202.1
c.535C>Ap.Leu179Met
missense
Exon 4 of 8ENSP00000543261.1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
31

ClinVar

ClinVar submissions
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP
Benign
0.0039
T
MetaRNN
Benign
0.060
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.90
L
PhyloP100
-0.29
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.40
N
REVEL
Benign
0.050
Sift
Benign
0.11
T
Sift4G
Benign
0.086
T
Polyphen
0.41
B
Vest4
0.090
MutPred
0.41
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
Mutation Taster
=95/5
polymorphism

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

Other links and lift over

dbSNP: rs1653235869; hg19: chr1-160460440; API