8-143159648-T-C
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Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The ENST00000615409.1(LY6H):āc.1A>Gā(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 (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 7.8e-7 ( 0 hom. )
Consequence
LY6H
ENST00000615409.1 start_lost
ENST00000615409.1 start_lost
Scores
3
2
11
Clinical Significance
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]
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ACMG classification
Classification made for transcript
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
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 7.78e-7 AC: 1AN: 1285782Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 630084
GnomAD4 exome
AF:
AC:
1
AN:
1285782
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
630084
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
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 | 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:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;.
REVEL
Benign
Sift
Pathogenic
D;D;D;.
Sift4G
Pathogenic
D;.;.;D
Polyphen
B;.;.;B
Vest4
MutPred
Loss of disorder (P = 0.105);.;.;Loss of disorder (P = 0.105);
MVP
MPC
0.42
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.