chr1-159952280-C-T

Variant names:

• chr1-159952280-C-T
• NM_033438.4:c.646G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_033438.4(SLAMF9):​c.646G>A​(p.Asp216Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLAMF9 NM_033438.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.37
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.646G>A	p.Asp216Asn	missense	Exon 3 of 4	NP_254273.2	Q96A28-1
	SLAMF9	NM_001146172.2		c.392-414G>A		intron	N/A	NP_001139644.1	Q96A28-2
	SLAMF9	NM_001146173.2		c.256-414G>A		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.646G>A	p.Asp216Asn	missense	Exon 3 of 4	ENSP00000357072.3	Q96A28-1
	SLAMF9	ENST00000368092.7	TSL:1	c.392-414G>A		intron	N/A	ENSP00000357071.3	Q96A28-2
	SLAMF9	ENST00000466773.5	TSL:3	n.303G>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.4
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.044
Sift	Benign	0.24	T
Sift4G	Benign	0.065	T
Polyphen		0.0	B
Vest4		0.26
MutPred		0.30		Gain of catalytic residue at D216 (P = 0.0467)
MVP		0.42
MPC		0.022
ClinPred		0.20	T
GERP RS		3.0
Varity_R		0.064
gMVP		0.21
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.21		Position offset: -18

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

Other links and lift over

hg19: chr1-159922070;