NM_020125.3:c.513C>G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.083238274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLAMF8	NM_020125.3	c.513C>G	p.Asp171Glu	missense_variant	Exon 3 of 5	ENST00000289707.10	NP_064510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLAMF8	ENST00000289707.10	c.513C>G	p.Asp171Glu	missense_variant	Exon 3 of 5	1	NM_020125.3	ENSP00000289707.5
SLAMF8	ENST00000368104.4	c.186C>G	p.Asp62Glu	missense_variant	Exon 2 of 4	2		ENSP00000357084.4
SLAMF8	ENST00000471286.5	n.331C>G		non_coding_transcript_exon_variant	Exon 2 of 4	3
SLAMF8	ENST00000497141.1	n.17C>G		non_coding_transcript_exon_variant	Exon 1 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 02, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.513C>G (p.D171E) alteration is located in exon 3 (coding exon 3) of the SLAMF8 gene. This alteration results from a C to G substitution at nucleotide position 513, causing the aspartic acid (D) at amino acid position 171 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.083	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.91	N;N
REVEL	Benign	0.051
Sift	Benign	0.12	T;T
Sift4G	Benign	0.31	T;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-159802811;