1-159952385-C-T

Variant names:

• chr1-159952385-C-T
• rs34884993
• NM_033438.4:c.541G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.016 (61 hom., cov: 31)
  • Exomes 𝑓: 0.0021 (71 hom.)
• Consequence: SLAMF9 NM_033438.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.181

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 Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLAMF9	NM_033438.4	c.541G>A	p.Glu181Lys	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.541G>A	p.Glu181Lys	missense_variant	Exon 3 of 4	1	NM_033438.4	ENSP00000357072.3
SLAMF9	ENST00000368092.7	c.392-519G>A		intron_variant	Intron 2 of 2	1		ENSP00000357071.3
SLAMF9	ENST00000466773.5	n.198G>A		non_coding_transcript_exon_variant	Exon 2 of 3	3
SLAMF9	ENST00000489098.1	n.303-519G>A		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 2490 AN: 152034 Hom.: 61 Cov.: 31

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

GnomAD3 exomes AF: 0.00472 AC: 1188 AN: 251464 Hom.: 24 AF XY: 0.00337 AC XY: 458 AN XY: 135906

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 SAS exome AF: 0.000229

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.: 71 Cov.: 33 AF XY: 0.00178 AC XY: 1295 AN XY: 727246

Gnomad4 AFR exome AF: 0.0641

Gnomad4 AMR exome AF: 0.00414

Gnomad4 ASJ exome AF: 0.00325

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000429

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000197

Gnomad4 OTH exome AF: 0.00518

GnomAD4 genome AF: 0.0164 AC: 2502 AN: 152152 Hom.: 61 Cov.: 31 AF XY: 0.0161 AC XY: 1194 AN XY: 74378

Gnomad4 AFR AF: 0.0559

Gnomad4 AMR AF: 0.00817

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.00330 Hom.: 24

Bravo AF: 0.0196

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0561 AC: 247

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00558 AC: 677

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0081	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.091
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.063
Sift	Benign	0.077	T
Sift4G	Benign	0.082	T
Polyphen		0.81	P
Vest4		0.43
MVP		0.58
MPC		0.19
ClinPred		0.037	T
GERP RS		4.0
Varity_R		0.17
gMVP		0.25

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: rs34884993; hg19: chr1-159922175;