1-159952318-T-C

Variant names:

• chr1-159952318-T-C
• rs754400365
• NM_033438.4:c.608A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_033438.4(SLAMF9):​c.608A>G​(p.Asn203Ser) 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLAMF9 NM_033438.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.360

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046785146).
• BP6: Variant 1-159952318-T-C is Benign according to our data. Variant chr1-159952318-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3162736.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLAMF9	NM_033438.4	c.608A>G	p.Asn203Ser	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.608A>G	p.Asn203Ser	missense_variant	Exon 3 of 4	1	NM_033438.4	ENSP00000357072.3
SLAMF9	ENST00000368092.7	c.392-452A>G		intron_variant	Intron 2 of 2	1		ENSP00000357071.3
SLAMF9	ENST00000466773.5	n.265A>G		non_coding_transcript_exon_variant	Exon 2 of 3	3
SLAMF9	ENST00000489098.1	n.303-452A>G		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251156 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135790

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 17, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.1
DANN	Benign	0.38
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-2.7	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.79	N
REVEL	Benign	0.019
Sift	Benign	0.95	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.21		Loss of catalytic residue at N203 (P = 0.0331);
MVP		0.19
MPC		0.021
ClinPred		0.029	T
GERP RS		0.67
Varity_R		0.028
gMVP		0.073

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

LitVar

Other links and lift over

dbSNP: rs754400365; hg19: chr1-159922108;