8-143158296-C-A

Variant names:

• chr8-143158296-C-A
• rs780038027
• NM_001135655.2:c.440G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001135655.2(LY6H):​c.440G>T​(p.Gly147Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G147E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LY6H NM_001135655.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• Publications: 3 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31537664).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135655.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LY6H	NM_001135655.2	MANE Select	c.440G>T	p.Gly147Val	missense	Exon 4 of 4	NP_001129127.1	O94772-2
	LY6H	NM_001130478.2		c.440G>T	p.Gly147Val	missense	Exon 5 of 5	NP_001123950.1	O94772-2
	LY6H	NM_002347.5		c.377G>T	p.Gly126Val	missense	Exon 4 of 4	NP_002338.3	O94772-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LY6H	ENST00000342752.9	TSL:1 MANE Select	c.440G>T	p.Gly147Val	missense	Exon 4 of 4	ENSP00000342711.4	O94772-2
	LY6H	ENST00000414417.6	TSL:1	c.440G>T	p.Gly147Val	missense	Exon 5 of 5	ENSP00000399485.2	O94772-2
	LY6H	ENST00000615409.1	TSL:1	c.377G>T	p.Gly126Val	missense	Exon 5 of 5	ENSP00000480084.1	O94772-1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461252 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726920

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53048

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111824

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.044	N
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.94	L
PhyloP100		-0.16
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.18
Sift	Benign	0.23	T
Sift4G	Uncertain	0.011	D
Polyphen		0.54	P
Vest4		0.52
MutPred		0.47		Gain of helix (P = 0.0349)
MVP		0.51
MPC		0.52
ClinPred		0.19	T
GERP RS		3.3
Varity_R		0.23
gMVP		0.68
Mutation Taster		=84/16	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

Other links and lift over

dbSNP: rs780038027; hg19: chr8-144239713; COSMIC: COSV61370694;