Variant 8-142700588-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017527.4(LY6K):c.61C>G(p.Leu21Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000028 in 1,426,930 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: -0.302

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037744284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY6K	NM_017527.4 linkuse as main transcript	c.61C>G	p.Leu21Val	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.61C>G	p.Leu21Val	missense_variant	1/3	1	NM_017527.4	ENSP00000292430.6	Q17RY6-1
LY6K	ENST00000519387.1 linkuse as main transcript	c.61C>G	p.Leu21Val	missense_variant	1/3	2		ENSP00000429695.1	Q17RY6-2
LY6K	ENST00000518841.5 linkuse as main transcript	c.61C>G	p.Leu21Val	missense_variant	1/3	2		ENSP00000427749.1	E5RGJ8
LY6K	ENST00000522591.1 linkuse as main transcript	c.61C>G	p.Leu21Val	missense_variant	1/2	2		ENSP00000428432.1	H0YB07

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000280

AC:

AN:

1426930

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

709022

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:

0.00000365

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

Nov 30, 2022

The c.61C>G (p.L21V) alteration is located in exon 1 (coding exon 1) of the LY6K gene. This alteration results from a C to G substitution at nucleotide position 61, causing the leucine (L) at amino acid position 21 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.032

DANN

Benign

0.91

DEOGEN2

Benign

0.0074

T;.;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0025

LIST_S2

Benign

0.47

T;T;T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.038

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.060

N;.;N;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.22

N;N;N;N

REVEL

Benign

0.0080

Sift

Benign

0.70

T;D;D;D

Sift4G

Benign

0.42

T;T;T;T

Polyphen

0.013

B;.;.;.

Vest4

0.019

MutPred

0.16

Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);

MVP

0.014

MPC

0.14

ClinPred

0.045

GERP RS

-2.2

Varity_R

0.033

gMVP

0.33

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over