1-159952436-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_033438.4(SLAMF9):​c.490G>T​(p.Asp164Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D164H) has been classified as Benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: SLAMF9 NM_033438.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 3 publications found

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]

LINC01133 (HGNC:49447): (long intergenic non-protein coding RNA 1133)

LOC124904438 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.773

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLAMF9	NM_033438.4	MANE Select	c.490G>T	p.Asp164Tyr	missense	Exon 3 of 4	NP_254273.2	Q96A28-1
	SLAMF9	NM_001146172.2		c.392-570G>T		intron	N/A	NP_001139644.1	Q96A28-2
	SLAMF9	NM_001146173.2		c.256-570G>T		intron	N/A	NP_001139645.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLAMF9	ENST00000368093.4	TSL:1 MANE Select	c.490G>T	p.Asp164Tyr	missense	Exon 3 of 4	ENSP00000357072.3	Q96A28-1
	SLAMF9	ENST00000368092.7	TSL:1	c.392-570G>T		intron	N/A	ENSP00000357071.3	Q96A28-2
	SLAMF9	ENST00000466773.5	TSL:3	n.147G>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152096 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251380 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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 Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1 AN XY: 74418

African (AFR) AF: 0.00 AC: 0 AN: 41522

American (AMR) AF: 0.0000654 AC: 1 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2112

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.081	T
Eigen	Benign	-0.039
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.0
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.11
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.75
MutPred		0.46		Gain of phosphorylation at D164 (P = 0.0394)
MVP		0.65
MPC		0.19
ClinPred		0.98	D
GERP RS		3.0
Varity_R		0.18
gMVP		0.42
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs35438196; hg19: chr1-159922226;