Variant 6-31672085-T-C 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.409T>C(p.Tyr137His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,460,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

LY6G5B
NM_021221.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

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=0.18266335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LY6G5B	NM_021221.3 link	c.409T>C	p.Tyr137His	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.409T>C	p.Tyr137His	missense_variant	Exon 3 of 3	1	NM_021221.3	ENSP00000365024.4		Q8NDX9-1
ENSG00000263020	ENST00000375880.6 link	c.*221T>C		3_prime_UTR_variant	Exon 8 of 8	3		ENSP00000365040.2		Q5SRQ3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246572

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134384

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000904

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1460818

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726722

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000848

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.409T>C (p.Y137H) alteration is located in exon 3 (coding exon 3) of the LY6G5B gene. This alteration results from a T to C substitution at nucleotide position 409, causing the tyrosine (Y) at amino acid position 137 to be replaced by a histidine (H). 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

Uncertain

0.51

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

.;.;T;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.79

T;T;T;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.18

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

.;.;M;.

PROVEAN

Benign

-2.4

.;.;N;D

REVEL

Benign

0.092

Sift

Pathogenic

0.0

.;.;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.25

.;.;B;.

Vest4

0.47

MutPred

0.62

.;.;Gain of disorder (P = 0.0153);.;

MVP

0.081

MPC

0.56

ClinPred

0.66

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.039

gMVP

0.42

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