chr8-143159648-T-C

Position:

• chr8-143159648-T-C

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The ENST00000615409.1(LY6H):​c.1A>G​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000778 in 1,285,782 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: LY6H ENST00000615409.1 start_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.37

Genes affected

LY6H (HGNC:6728): (lymphocyte antigen 6 family member H) Predicted to enable acetylcholine receptor binding activity and acetylcholine receptor inhibitor activity. Predicted to be involved in acetylcholine receptor signaling pathway. Predicted to be located in extracellular region. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LY6H	NM_001135655.2	c.64A>G	p.Met22Val	missense_variant	2/4	ENST00000342752.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LY6H	ENST00000342752.9	c.64A>G	p.Met22Val	missense_variant	2/4	1	NM_001135655.2	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.78e-7 AC: 1 AN: 1285782 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 630084

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: 9.63e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2021

The c.64A>G (p.M22V) alteration is located in exon 3 (coding exon 2) of the LY6H gene. This alteration results from a A to G substitution at nucleotide position 64, causing the methionine (M) at amino acid position 22 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
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.023	T;.;.;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.26	N
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.73	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.56	N;N;N;.
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D;D;D;.
Sift4G	Pathogenic	0.0	D;.;.;D
Polyphen		0.017	B;.;.;B
Vest4		0.74
MutPred		1.0		Loss of disorder (P = 0.105);.;.;Loss of disorder (P = 0.105);
MVP		0.47
MPC		0.42
ClinPred		0.24	T
GERP RS		2.2
Varity_R		0.85
gMVP		0.63

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.

Other links and lift over

hg19: chr8-144241065;