1-159952436-C-G

Variant names:

• chr1-159952436-C-G
• rs35438196
• NM_033438.4:c.490G>C

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.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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.017 (68 hom., cov: 31)
  • Exomes 𝑓: 0.0018 (63 hom.)
• Consequence: SLAMF9 NM_033438.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.00

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=0.0047166646).
• 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 rank	MANE	Protein	UniProt
SLAMF9	NM_033438.4	c.490G>C	p.Asp164His	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.490G>C	p.Asp164His	missense_variant	Exon 3 of 4	1	NM_033438.4	ENSP00000357072.3
SLAMF9	ENST00000368092.7	c.392-570G>C		intron_variant	Intron 2 of 2	1		ENSP00000357071.3
SLAMF9	ENST00000466773.5	n.147G>C		non_coding_transcript_exon_variant	Exon 2 of 3	3
SLAMF9	ENST00000489098.1	n.303-570G>C		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2518 AN: 152090 Hom.: 68 Cov.: 31

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.: 31 AF XY: 0.00364 AC XY: 495 AN XY: 135846

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.: 63 Cov.: 33 AF XY: 0.00166 AC XY: 1207 AN XY: 727248

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.: 68 Cov.: 31 AF XY: 0.0165 AC XY: 1227 AN XY: 74414

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.: 5

Bravo AF: 0.0181

ESP6500AA AF: 0.0542 AC: 239

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00549 AC: 667

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000218

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 20, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.090
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.032
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.59
MVP		0.54
MPC		0.19
ClinPred		0.039	T
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

Other links and lift over

dbSNP: rs35438196; hg19: chr1-159922226;