Genetic Variant SLAMF9:p.Asn203Ser (chr1-159952318-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_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. 16/22 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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.360

Publications

0 publications found

Variant links:

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]

SLAMF9 links:

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

LINC01133 links:

LOC124904438 (HGNC:):

LOC124904438 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 3162736.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLAMF9	NM_033438.4	MANE Select	c.608A>G	p.Asn203Ser	missense	Exon 3 of 4	NP_254273.2	Q96A28-1
SLAMF9	NM_001146172.2		c.392-452A>G		intron	N/A	NP_001139644.1	Q96A28-2
SLAMF9	NM_001146173.2		c.256-452A>G		intron	N/A	NP_001139645.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLAMF9	ENST00000368093.4	TSL:1 MANE Select	c.608A>G	p.Asn203Ser	missense	Exon 3 of 4	ENSP00000357072.3	Q96A28-1
SLAMF9	ENST00000368092.7	TSL:1	c.392-452A>G		intron	N/A	ENSP00000357071.3	Q96A28-2
SLAMF9	ENST00000466773.5	TSL:3	n.265A>G		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251156

AF XY:

0.00000736

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.1

(source)

DANN

Benign

0.38

DEOGEN2

Benign

0.0016

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0044

LIST_S2

Benign

0.54

M_CAP

Benign

0.0052

MetaRNN

Benign

0.047

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.7

PhyloP100

-0.36

PrimateAI

Benign

0.29

PROVEAN

Benign

0.79

REVEL

Benign

0.019

Sift

Benign

0.95

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.17

MutPred

0.21

Loss of catalytic residue at N203 (P = 0.0331)

MVP

0.19

MPC

0.021

ClinPred

0.029

GERP RS

0.67

Varity_R

0.028

gMVP

0.073

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over