NM_001184714.2:c.943T>C

Variant names:

• chr1-160487112-A-G
• rs1272020742
• NM_001184714.2:c.943T>C

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.943T>C​(p.Ser315Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. S315A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLAMF6 NM_001184714.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940
• Publications: 1 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=0.043825656).

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.943T>C	p.Ser315Pro	missense	Exon 7 of 8	NP_001171643.1	Q96DU3-1
	SLAMF6	NM_052931.5		c.940T>C	p.Ser314Pro	missense	Exon 7 of 8	NP_443163.1	Q96DU3-2
	SLAMF6	NM_001184715.2		c.793T>C	p.Ser265Pro	missense	Exon 7 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.943T>C	p.Ser315Pro	missense	Exon 7 of 8	ENSP00000357036.3	Q96DU3-1
	SLAMF6	ENST00000368059.7	TSL:1	c.940T>C	p.Ser314Pro	missense	Exon 7 of 8	ENSP00000357038.3	Q96DU3-2
	SLAMF6	ENST00000873203.1		c.832T>C	p.Ser278Pro	missense	Exon 6 of 7	ENSP00000543262.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250824 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459886 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726402

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 86160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110492

Other (OTH) AF: 0.0000331 AC: 2 AN: 60346

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0448430), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.84
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0086	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.094
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.040
Sift	Benign	0.094	T
Sift4G	Benign	0.10	T
Polyphen		0.26	B
Vest4		0.12
MutPred		0.19		Gain of sheet (P = 0.0266)
MVP		0.18
MPC		0.40
ClinPred		0.13	T
GERP RS		-2.6
Varity_R		0.19
gMVP		0.17
Mutation Taster		=72/28	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: rs1272020742; hg19: chr1-160456902;