1-159829898-G-C

Variant names:

• chr1-159829898-G-C
• rs762647287
• NM_020125.3:c.73G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020125.3(SLAMF8):​c.73G>C​(p.Val25Leu) 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 1,461,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. V25M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLAMF8 NM_020125.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75
• Publications: 0 publications found

Genes affected

SLAMF8 (HGNC:21391): (SLAM family member 8) This gene encodes a member of the CD2 family of cell surface proteins involved in lymphocyte activation. These proteins are characterized by Ig domains. This protein is expressed in lymphoid tissues, and studies of a similar protein in mouse suggest that it may function during B cell lineage commitment. The gene is found in a region of chromosome 1 containing many CD2 genes. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21569979).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020125.3. 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
	SLAMF8	NM_020125.3	MANE Select	c.73G>C	p.Val25Leu	missense	Exon 2 of 5	NP_064510.1	Q9P0V8-1
	SLAMF8	NM_001330741.2		c.40+2960G>C		intron	N/A	NP_001317670.1	Q9P0V8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLAMF8	ENST00000289707.10	TSL:1 MANE Select	c.73G>C	p.Val25Leu	missense	Exon 2 of 5	ENSP00000289707.5	Q9P0V8-1
	SLAMF8	ENST00000852920.1		c.73G>C	p.Val25Leu	missense	Exon 2 of 5	ENSP00000522979.1
	SLAMF8	ENST00000852921.1		c.55G>C	p.Val19Leu	missense	Exon 2 of 5	ENSP00000522980.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461358 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726970

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111738

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.7
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.088
Sift	Benign	0.18	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.36	B
Vest4		0.48
MutPred		0.51		Loss of ubiquitination at K28 (P = 0.0982)
MVP		0.12
MPC		0.077
ClinPred		0.46	T
GERP RS		3.5
Varity_R		0.067
gMVP		0.43
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: rs762647287; hg19: chr1-159799688;