Genetic Variant SLAMF7:p.Gln255Lys (chr1-160750417-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021181.5(SLAMF7):c.763C>A(p.Gln255Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000253 in 1,461,154 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

SLAMF7
NM_021181.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.24

Publications

1 publications found

Variant links:

Genes affected

SLAMF7 (HGNC:21394): (SLAM family member 7) Enables identical protein binding activity. Predicted to be involved in adaptive immune response. Predicted to act upstream of or within regulation of natural killer cell activation. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

SLAMF7 links:

ENSG00000303180 (HGNC:):

ENSG00000303180 links:

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ACMG classification

Classification was made for transcript

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=0.03313932).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021181.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLAMF7	NM_021181.5	MANE Select	c.763C>A	p.Gln255Lys	missense	Exon 4 of 7	NP_067004.3
SLAMF7	NM_001282592.2		c.763C>A	p.Gln255Lys	missense	Exon 4 of 6	NP_001269521.1	Q9NQ25-5
SLAMF7	NM_001282594.2		c.481C>A	p.Gln161Lys	missense	Exon 3 of 6	NP_001269523.1	B4DW98

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLAMF7	ENST00000368043.8	TSL:1 MANE Select	c.763C>A	p.Gln255Lys	missense	Exon 4 of 7	ENSP00000357022.3	Q9NQ25-1
SLAMF7	ENST00000359331.8	TSL:1	c.763C>A	p.Gln255Lys	missense	Exon 4 of 6	ENSP00000352281.4	Q9NQ25-5
SLAMF7	ENST00000368042.7	TSL:1	c.442C>A	p.Gln148Lys	missense	Exon 3 of 6	ENSP00000357021.3	Q9NQ25-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

250306

AF XY:

0.00000740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1461154

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

726896

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33442

American (AMR)

AF:

0.0000224

AC:

AN:

44570

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86174

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000270

AC:

AN:

1111668

Other (OTH)

AF:

0.0000497

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.061

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.0070

(source)

DANN

Benign

0.23

DEOGEN2

Benign

0.11

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0044

LIST_S2

Benign

0.35

M_CAP

Benign

0.0037

MetaRNN

Benign

0.033

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PhyloP100

-1.2

PrimateAI

Benign

0.24

PROVEAN

Benign

0.060

REVEL

Benign

0.013

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0040

Vest4

0.099

MutPred

0.31

Gain of methylation at Q255 (P = 0.0098)

MVP

0.20

MPC

0.20

ClinPred

0.019

GERP RS

-5.9

Varity_R

0.046

gMVP

0.31

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over