6-6588741-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004271.4(LY86):c.7G>T(p.Gly3Cys) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LY86 NM_004271.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.111

Genes affected

LY86 (HGNC:16837): (lymphocyte antigen 86) Acts upstream of or within positive regulation of lipopolysaccharide-mediated signaling pathway. Predicted to be located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

LY86-AS1 (HGNC:26593): (LY86 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34602615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LY86	NM_004271.4	c.7G>T	p.Gly3Cys	missense_variant	1/5	ENST00000230568.5
LY86-AS1	NR_026970.1	n.196-19252C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LY86	ENST00000230568.5	c.7G>T	p.Gly3Cys	missense_variant	1/5	1	NM_004271.4	P1
LY86-AS1	ENST00000429345.5	n.114-19252C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Aug 08, 2022

The c.7G>T (p.G3C) alteration is located in exon 1 (coding exon 1) of the LY86 gene. This alteration results from a G to T substitution at nucleotide position 7, causing the glycine (G) at amino acid position 3 to be replaced by a cysteine (C). 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	0.19
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	16
Dann	Uncertain	0.99
DEOGEN2	Benign	0.26	T;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.031	N
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.12
Sift	Benign	0.057	T;T
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.95	P;P
Vest4		0.43
MutPred		0.48		Gain of catalytic residue at M1 (P = 0.0044);Gain of catalytic residue at M1 (P = 0.0044);
MVP		0.72
MPC		0.028
ClinPred		0.53	D
GERP RS		2.3
Varity_R		0.13
gMVP		0.41

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: chr6-6588974;