1-160796285-A-C

Position:

• chr1-160796285-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002348.4(LY9):​c.98A>C​(p.Gln33Pro) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LY9 NM_002348.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.851

Genes affected

LY9 (HGNC:6730): (lymphocyte antigen 9) LY9 belongs to the SLAM family of immunomodulatory receptors (see SLAMF1; MIM 603492) and interacts with the adaptor molecule SAP (SH2D1A; MIM 300490) (Graham et al., 2006 [PubMed 16365421]).[supplied by OMIM, Mar 2008]

LY9 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17006955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY9	NM_002348.4	c.98A>C	p.Gln33Pro	missense_variant	1/10	ENST00000263285.11	NP_002339.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LY9	ENST00000263285.11	c.98A>C	p.Gln33Pro	missense_variant	1/10	1	NM_002348.4	ENSP00000263285.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Oct 12, 2022

The c.98A>C (p.Q33P) alteration is located in exon 1 (coding exon 1) of the LY9 gene. This alteration results from a A to C substitution at nucleotide position 98, causing the glutamine (Q) at amino acid position 33 to be replaced by a proline (P). 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	0.080
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Benign	0.73
DEOGEN2	Benign	0.081	.;.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.71	T;T;T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.0	.;.;N;N
REVEL	Benign	0.027
Sift	Uncertain	0.011	.;.;D;D
Sift4G	Uncertain	0.031	D;D;D;T
Polyphen		0.0090	B;.;B;.
Vest4		0.37
MutPred		0.62		Loss of catalytic residue at Q33 (P = 0.1316);Loss of catalytic residue at Q33 (P = 0.1316);Loss of catalytic residue at Q33 (P = 0.1316);Loss of catalytic residue at Q33 (P = 0.1316);
MVP		0.38
MPC		0.14
ClinPred		0.036	T
GERP RS		1.2
Varity_R		0.21
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-160766075;