1-159952408-C-A

Variant names:

• chr1-159952408-C-A
• NM_033438.4:c.518G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033438.4(SLAMF9):​c.518G>T​(p.Gly173Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLAMF9 NM_033438.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.997

Genes affected

SLAMF9 (HGNC:18430): (SLAM family member 9) This gene encodes a member of the signaling lymphocytic activation molecule family. The encoded protein is a cell surface molecule that consists of two extracellular immunoglobulin domains, a transmembrane domain and a short cytoplasmic tail that lacks the signal transduction motifs found in other family members. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Apr 2009]

LOC124904438 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLAMF9	NM_033438.4	c.518G>T	p.Gly173Val	missense_variant	Exon 3 of 4	ENST00000368093.4	NP_254273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLAMF9	ENST00000368093.4	c.518G>T	p.Gly173Val	missense_variant	Exon 3 of 4	1	NM_033438.4	ENSP00000357072.3
SLAMF9	ENST00000368092.7	c.392-542G>T		intron_variant	Intron 2 of 2	1		ENSP00000357071.3
SLAMF9	ENST00000466773.5	n.175G>T		non_coding_transcript_exon_variant	Exon 2 of 3	3
SLAMF9	ENST00000489098.1	n.303-542G>T		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.518G>T (p.G173V) alteration is located in exon 3 (coding exon 3) of the SLAMF9 gene. This alteration results from a G to T substitution at nucleotide position 518, causing the glycine (G) at amino acid position 173 to be replaced by a valine (V). 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	0.13
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Pathogenic	2.9	M
PrimateAI	Benign	0.21	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.11
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.050	T
Polyphen		0.99	D
Vest4		0.43
MutPred		0.61		Loss of disorder (P = 0.0602);
MVP		0.58
MPC		0.17
ClinPred		0.98	D
GERP RS		-3.0
Varity_R		0.15
gMVP		0.46

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-159922198;