8-142703174-C-T

Variant names:

• chr8-142703174-C-T
• rs151035945
• NM_017527.4:c.301C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017527.4(LY6K):​c.301C>T​(p.Arg101Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000756 in 1,614,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000076 (0 hom.)
• Consequence: LY6K NM_017527.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.10

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]

LNCOC1 (HGNC:53947): (lncRNA associated with ovarian cancer 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047512114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LY6K	NM_017527.4	c.301C>T	p.Arg101Trp	missense_variant	Exon 3 of 3	ENST00000292430.10	NP_059997.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LY6K	ENST00000292430.10	c.301C>T	p.Arg101Trp	missense_variant	Exon 3 of 3	1	NM_017527.4	ENSP00000292430.6

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000716 AC: 18 AN: 251482 AF XY: 0.0000809

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000105

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000759 AC: 111 AN: 1461882 Hom.: 0 Cov.: 34 AF XY: 0.0000880 AC XY: 64 AN XY: 727240

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.0000899 AC: 100 AN: 1112010

Other (OTH) AF: 0.0000994 AC: 6 AN: 60392

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152330 Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6 AN XY: 74490

African (AFR) AF: 0.0000481 AC: 2 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000118 Hom.: 0

Bravo AF: 0.0000604

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 22, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.301C>T (p.R101W) alteration is located in exon 3 (coding exon 3) of the LY6K gene. This alteration results from a C to T substitution at nucleotide position 301, causing the arginine (R) at amino acid position 101 to be replaced by a tryptophan (W). 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	0.13
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.20
DANN	Benign	0.84
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0059	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.94	T
PhyloP100		-4.1
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.0070
Sift	Pathogenic	0.0	D
Vest4		0.079
MVP		0.014
ClinPred		0.98	D
GERP RS		-5.8
Varity_R		0.067
Mutation Taster		=97/3	polymorphism

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

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Other links and lift over

dbSNP: rs151035945; hg19: chr8-143784592;