Genetic Variant SLAMF9:p.Glu181Lys (chr1-159952385-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033438.4(SLAMF9):c.541G>A(p.Glu181Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00343 in 1,614,036 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 61 hom., cov: 31)

Exomes 𝑓: 0.0021 ( 71 hom. )

Consequence

SLAMF9
NM_033438.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.181

Publications

4 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035706758).

BP6

Variant 1-159952385-C-T is Benign according to our data. Variant chr1-159952385-C-T is described in ClinVar as Benign. ClinVar VariationId is 782393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.054 is higher than 0.05.

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.541G>A	p.Glu181Lys	missense	Exon 3 of 4	NP_254273.2	Q96A28-1
SLAMF9	NM_001146172.2		c.392-519G>A		intron	N/A	NP_001139644.1	Q96A28-2
SLAMF9	NM_001146173.2		c.256-519G>A		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.541G>A	p.Glu181Lys	missense	Exon 3 of 4	ENSP00000357072.3	Q96A28-1
SLAMF9	ENST00000368092.7	TSL:1	c.392-519G>A		intron	N/A	ENSP00000357071.3	Q96A28-2
SLAMF9	ENST00000466773.5	TSL:3	n.198G>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.0164

AC:

2490

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0557

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00818

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.00472

AC:

1188

AN:

251464

AF XY:

0.00337

show subpopulations

Gnomad AFR exome

AF:

0.0602

Gnomad AMR exome

AF:

0.00338

Gnomad ASJ exome

AF:

0.00367

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00208

AC:

3035

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00178

AC XY:

1295

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.0641

AC:

2146

AN:

33480

American (AMR)

AF:

0.00414

AC:

185

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00325

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000429

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000197

AC:

219

AN:

1112004

Other (OTH)

AF:

0.00518

AC:

313

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

203

406

609

812

1015

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0164

AC:

2502

AN:

152152

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1194

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0559

AC:

2318

AN:

41458

American (AMR)

AF:

0.00817

AC:

125

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

67990

Other (OTH)

AF:

0.0151

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

113

226

338

451

564

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00675

Hom.:

Bravo

AF:

0.0196

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0561

AC:

247

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00558

AC:

677

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0081

Eigen

Benign

0.12

Eigen_PC

Benign

0.091

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0036

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PhyloP100

0.18

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.063

Sift

Benign

0.077

Sift4G

Benign

0.082

Polyphen

0.81

Vest4

0.43

MVP

0.58

MPC

0.19

ClinPred

0.037

GERP RS

4.0

Varity_R

0.17

gMVP

0.25

Mutation Taster

=97/3

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over