1-159951686-G-A

Variant names:

• chr1-159951686-G-A
• rs1199900747
• NM_033438.4:c.845C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033438.4(SLAMF9):​c.845C>T​(p.Ala282Val) 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. 15/22 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. A282E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLAMF9 NM_033438.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 0 publications found

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]

LINC01133 (HGNC:49447): (long intergenic non-protein coding RNA 1133)

LOC124904438 (HGNC:):

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=0.042465627).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033438.4. 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
	SLAMF9	NM_033438.4	MANE Select	c.845C>T	p.Ala282Val	missense	Exon 4 of 4	NP_254273.2	Q96A28-1
	SLAMF9	NM_001146172.2		c.572C>T	p.Ala191Val	missense	Exon 3 of 3	NP_001139644.1	Q96A28-2
	SLAMF9	NM_001146173.2		c.*100C>T		3_prime_UTR	Exon 3 of 3	NP_001139645.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLAMF9	ENST00000368093.4	TSL:1 MANE Select	c.845C>T	p.Ala282Val	missense	Exon 4 of 4	ENSP00000357072.3	Q96A28-1
	SLAMF9	ENST00000368092.7	TSL:1	c.572C>T	p.Ala191Val	missense	Exon 3 of 3	ENSP00000357071.3	Q96A28-2
	SLAMF9	ENST00000466773.5	TSL:3	n.502C>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.6
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.0050
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.056	T
Polyphen		0.0050	B
Vest4		0.15
MutPred		0.12		Loss of ubiquitination at K277 (P = 0.1202)
MVP		0.17
MPC		0.031
ClinPred		0.30	T
GERP RS		-5.1
Varity_R		0.032
gMVP		0.14
Mutation Taster		=100/0	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: rs1199900747; hg19: chr1-159921476;