chr1-159833021-C-G

Variant names:

• chr1-159833021-C-G
• NM_020125.3:c.513C>G

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.513C>G​(p.Asp171Glu) 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: 32)
• Consequence: SLAMF8 NM_020125.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0770
• 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=0.083238274).

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.513C>G	p.Asp171Glu	missense	Exon 3 of 5	NP_064510.1	Q9P0V8-1
	SLAMF8	NM_001330741.2		c.186C>G	p.Asp62Glu	missense	Exon 2 of 4	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.513C>G	p.Asp171Glu	missense	Exon 3 of 5	ENSP00000289707.5	Q9P0V8-1
	SLAMF8	ENST00000852920.1		c.513C>G	p.Asp171Glu	missense	Exon 3 of 5	ENSP00000522979.1
	SLAMF8	ENST00000852921.1		c.495C>G	p.Asp165Glu	missense	Exon 3 of 5	ENSP00000522980.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.4
DANN	Benign	0.92
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.077
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.051
Sift	Benign	0.12	T
Sift4G	Benign	0.31	T
Polyphen		0.051	B
Vest4		0.13
MutPred		0.29		Gain of disorder (P = 0.0819)
MVP		0.21
MPC		0.058
ClinPred		0.092	T
GERP RS		3.6
Varity_R		0.10
gMVP		0.16
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr1-159802811;