8-143158296-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001135655.2(LY6H):​c.440G>A​(p.Gly147Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,328 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: LY6H NM_001135655.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>A	p.Gly147Glu	missense	Exon 4 of 4	NP_001129127.1	O94772-2
	LY6H	NM_001130478.2		c.440G>A	p.Gly147Glu	missense	Exon 5 of 5	NP_001123950.1	O94772-2
	LY6H	NM_002347.5		c.377G>A	p.Gly126Glu	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>A	p.Gly147Glu	missense	Exon 4 of 4	ENSP00000342711.4	O94772-2
	LY6H	ENST00000414417.6	TSL:1	c.440G>A	p.Gly147Glu	missense	Exon 5 of 5	ENSP00000399485.2	O94772-2
	LY6H	ENST00000615409.1	TSL:1	c.377G>A	p.Gly126Glu	missense	Exon 5 of 5	ENSP00000480084.1	O94772-1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152076 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000242 AC: 6 AN: 248130 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000537

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000397 AC: 58 AN: 1461252 Hom.: 0 Cov.: 34 AF XY: 0.0000358 AC XY: 26 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: 0.0000252 AC: 1 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: 0.0000513 AC: 57 AN: 1111824

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

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152076 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74266

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000825 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.028	N
M_CAP	Benign	0.0062	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.16
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.14
Sift	Benign	0.16	T
Sift4G	Uncertain	0.0060	D
Polyphen		0.36	B
Vest4		0.62
MVP		0.53
MPC		0.54
ClinPred		0.19	T
GERP RS		3.3
Varity_R		0.31
gMVP		0.77
Mutation Taster		=91/9	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: COSV61370351;