chr1-159952280-C-T

Position:

• chr1-159952280-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000368093.4(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. 14/23 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 ENST00000368093.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.37

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLAMF9	NM_033438.4	c.646G>A	p.Asp216Asn	missense_variant	3/4	ENST00000368093.4	NP_254273.2
LOC124904438	XR_007066684.1	n.380-1297C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLAMF9	ENST00000368093.4	c.646G>A	p.Asp216Asn	missense_variant	3/4	1	NM_033438.4	ENSP00000357072	P1
SLAMF9	ENST00000368092.7	c.392-414G>A		intron_variant		1		ENSP00000357071
SLAMF9	ENST00000466773.5	n.303G>A		non_coding_transcript_exon_variant	2/3	3
SLAMF9	ENST00000489098.1	n.303-414G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2024

The c.646G>A (p.D216N) alteration is located in exon 3 (coding exon 3) of the SLAMF9 gene. This alteration results from a G to A substitution at nucleotide position 646, causing the aspartic acid (D) at amino acid position 216 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	N;N
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-159922070;