Variant 6-31671929-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021221.3(LY6G5B):c.253C>T(p.Arg85Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,460,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

LY6G5B
NM_021221.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.354

Variant links:

Genes affected

LY6G5B (HGNC:13931): (lymphocyte antigen 6 family member G5B) LY6G5B belongs to a cluster of leukocyte antigen-6 (LY6) genes located in the major histocompatibility complex (MHC) class III region on chromosome 6. Members of the LY6 superfamily typically contain 70 to 80 amino acids, including 8 to 10 cysteines. Most LY6 proteins are attached to the cell surface by a glycosylphosphatidylinositol (GPI) anchor that is directly involved in signal transduction (Mallya et al., 2002 [PubMed 12079290]).[supplied by OMIM, Mar 2008]

LY6G5B links:

ENSG00000263020 (HGNC:):

ENSG00000263020 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.1381751).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LY6G5B	NM_021221.3 link	c.253C>T	p.Arg85Cys	missense_variant	Exon 3 of 3	ENST00000375864.5	NP_067044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LY6G5B	ENST00000375864.5 link	c.253C>T	p.Arg85Cys	missense_variant	Exon 3 of 3	1	NM_021221.3	ENSP00000365024.4		Q8NDX9-1
ENSG00000263020	ENST00000375880.6 link	c.*65C>T		3_prime_UTR_variant	Exon 8 of 8	3		ENSP00000365040.2		Q5SRQ3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

246662

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134408

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000903

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1460804

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726714

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000338

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.253C>T (p.R85C) alteration is located in exon 3 (coding exon 3) of the LY6G5B gene. This alteration results from a C to T substitution at nucleotide position 253, causing the arginine (R) at amino acid position 85 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

0.18

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

.;.;T;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.12

LIST_S2

Uncertain

0.86

D;D;D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.8

.;.;L;.

PROVEAN

Pathogenic

-5.2

.;.;D;D

REVEL

Benign

0.11

Sift

Uncertain

0.0020

.;.;D;D

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

1.0

.;.;D;.

Vest4

0.17

MutPred

0.27

.;.;Loss of sheet (P = 0.0054);.;

MVP

0.48

MPC

0.16

ClinPred

0.55

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over