rs1187779262

Variant names:

• chr6-35805715-T-A
• rs1187779262
• NM_182548.4:c.45T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-35805715-T-A
• chr6-35805715-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_182548.4(LHFPL5):​c.45T>A​(p.His15Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LHFPL5 NM_182548.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

Genes affected

LHFPL5 (HGNC:21253): (LHFPL tetraspan subfamily member 5) This gene is a member of the lipoma HMGIC fusion partner (LHFP) gene family, which is a subset of the superfamily of tetraspan transmembrane protein encoding genes. Mutations in this gene result in deafness in humans, and a mutation in a similar gene in mice results in deafness and vestibular dysfunction with severe degeneration of the organ of Corti. It is proposed to function in hair bundle morphogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a chain LHFPL tetraspan subfamily member 5 protein (size 218) in uniprot entity LHPL5_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_182548.4
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.749

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHFPL5	NM_182548.4	c.45T>A	p.His15Gln	missense_variant	Exon 1 of 4	ENST00000360215.3	NP_872354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHFPL5	ENST00000360215.3	c.45T>A	p.His15Gln	missense_variant	Exon 1 of 4	1	NM_182548.4	ENSP00000353346.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.31	T;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.42	N
LIST_S2	Uncertain	0.87	.;D
M_CAP	Uncertain	0.088	D
MetaRNN	Pathogenic	0.75	D;D
MetaSVM	Benign	-0.40	T
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.9	D;.
REVEL	Uncertain	0.51
Sift	Benign	0.47	T;.
Sift4G	Benign	0.43	T;.
Polyphen		0.99	D;D
Vest4		0.82
MutPred		0.50		Gain of catalytic residue at H15 (P = 0.0474);Gain of catalytic residue at H15 (P = 0.0474);
MVP		0.31
MPC		1.0
ClinPred		0.94	D
GERP RS		-5.1
Varity_R		0.26

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

LitVar

Other links and lift over

dbSNP: rs1187779262; hg19: chr6-35773492;