Variant 8-142700573-T-A 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_017527.4(LY6K):c.46T>A(p.Trp16Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,433,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

LY6K
NM_017527.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.196

Variant links:

Genes affected

LY6K (HGNC:24225): (lymphocyte antigen 6 family member K) Predicted to be involved in binding activity of sperm to zona pellucida. Predicted to act upstream of or within flagellated sperm motility. Predicted to be located in cell surface; cytoplasm; and plasma membrane. Predicted to be active in acrosomal vesicle. [provided by Alliance of Genome Resources, Apr 2022]

LY6K links:

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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=0.08434698).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY6K	NM_017527.4 linkuse as main transcript	c.46T>A	p.Trp16Arg	missense_variant	1/3	ENST00000292430.10	NP_059997.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LY6K	ENST00000292430.10 linkuse as main transcript	c.46T>A	p.Trp16Arg	missense_variant	1/3	1	NM_017527.4	ENSP00000292430.6	Q17RY6-1
LY6K	ENST00000519387.1 linkuse as main transcript	c.46T>A	p.Trp16Arg	missense_variant	1/3	2		ENSP00000429695.1	Q17RY6-2
LY6K	ENST00000518841.5 linkuse as main transcript	c.46T>A	p.Trp16Arg	missense_variant	1/3	2		ENSP00000427749.1	E5RGJ8
LY6K	ENST00000522591.1 linkuse as main transcript	c.46T>A	p.Trp16Arg	missense_variant	1/2	2		ENSP00000428432.1	H0YB07

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000143

AC:

AN:

209862

Hom.:

AF XY:

0.0000260

AC XY:

AN XY:

115588

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000648

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:

0.00

Gnomad OTH exome

AF:

0.000199

GnomAD4 exome

AF:

0.00000279

AC:

AN:

1433686

Hom.:

Cov.:

AF XY:

0.00000421

AC XY:

AN XY:

712320

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000949

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 24, 2024

The c.46T>A (p.W16R) alteration is located in exon 1 (coding exon 1) of the LY6K gene. This alteration results from a T to A substitution at nucleotide position 46, causing the tryptophan (W) at amino acid position 16 to be replaced by an arginine (R). 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

0.32

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.3

DANN

Benign

0.82

DEOGEN2

Benign

0.091

T;.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0063

LIST_S2

Benign

0.31

T;T;T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.084

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.76

N;.;N;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.9

N;D;D;D

REVEL

Benign

0.059

Sift

Benign

0.12

T;D;D;D

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.87

P;.;.;.

Vest4

0.052

MutPred

0.61

Gain of disorder (P = 8e-04);Gain of disorder (P = 8e-04);Gain of disorder (P = 8e-04);Gain of disorder (P = 8e-04);

MVP

0.030

MPC

0.34

ClinPred

0.055

GERP RS

-2.5

Varity_R

0.11

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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