Variant 1-159952436-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033438.4(SLAMF9):c.490G>C(p.Asp164His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00323 in 1,614,088 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.017 ( 68 hom., cov: 31)

Exomes 𝑓: 0.0018 ( 63 hom. )

Consequence

SLAMF9
NM_033438.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.00

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:

SLAMF9 (HGNC:):

SLAMF9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047166646).

BP6

Variant 1-159952436-C-G is Benign according to our data. Variant chr1-159952436-C-G is described in ClinVar as [Benign]. Clinvar id is 709553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLAMF9	NM_033438.4 linkuse as main transcript	c.490G>C	p.Asp164His	missense_variant	3/4	ENST00000368093.4	NP_254273.2	Q96A28-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLAMF9	ENST00000368093.4 linkuse as main transcript	c.490G>C	p.Asp164His	missense_variant	3/4	1	NM_033438.4	ENSP00000357072.3	Q96A28-1
SLAMF9	ENST00000368092.7 linkuse as main transcript	c.392-570G>C		intron_variant		1		ENSP00000357071.3	Q96A28-2
SLAMF9	ENST00000466773.5 linkuse as main transcript	n.147G>C		non_coding_transcript_exon_variant	2/3	3
SLAMF9	ENST00000489098.1 linkuse as main transcript	n.303-570G>C		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0166

AC:

2518

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0573

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00543

Gnomad ASJ

AF:

0.00721

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00451

AC:

1134

AN:

251380

Hom.:

AF XY:

0.00364

AC XY:

495

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.0581

Gnomad AMR exome

AF:

0.00217

Gnomad ASJ exome

AF:

0.00714

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00184

AC:

2691

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

1207

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0585

Gnomad4 AMR exome

AF:

0.00241

Gnomad4 ASJ exome

AF:

0.00807

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000854

Gnomad4 OTH exome

AF:

0.00424

GnomAD4 genome

AF:

0.0166

AC:

2526

AN:

152208

Hom.:

Cov.:

AF XY:

0.0165

AC XY:

1227

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0574

Gnomad4 AMR

AF:

0.00543

Gnomad4 ASJ

AF:

0.00721

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00329

Hom.:

Bravo

AF:

0.0181

ESP6500AA

AF:

0.0542

AC:

239

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00549

AC:

667

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.060

Eigen

Benign

-0.090

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0047

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.032

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.59

MVP

0.54

MPC

0.19

ClinPred

0.039

GERP RS

3.0

Varity_R

0.14

gMVP

0.32

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over