rs1315573645

Variant names:

• chrX-112631437-G-A
• NM_178175.4:c.646C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-112631437-G-A
• chrX-112631437-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178175.4(LHFPL1):​c.646C>T​(p.His216Tyr) 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 benign outcome for this variant. 14/20 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. H216N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: LHFPL1 NM_178175.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41

Genes affected

LHFPL1 (HGNC:6587): (LHFPL tetraspan subfamily member 1) 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 one LHFP-like gene result in deafness in humans and mice, and a second LHFP-like gene is fused to a high-mobility group gene in a translocation-associated lipoma. Alternatively spliced transcript variants have been found, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11348522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHFPL1	NM_178175.4	c.646C>T	p.His216Tyr	missense_variant	Exon 4 of 4	ENST00000371968.8	NP_835469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHFPL1	ENST00000371968.8	c.646C>T	p.His216Tyr	missense_variant	Exon 4 of 4	1	NM_178175.4	ENSP00000361036.3
LHFPL1	ENST00000478229.1	n.466C>T		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.016	T
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.58	T
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.031
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.025	D
Polyphen		0.45	B
Vest4		0.16
MutPred		0.24		Loss of disorder (P = 0.0487);
MVP		0.43
MPC		0.15
ClinPred		0.47	T
GERP RS		3.5
Varity_R		0.14
gMVP		0.56

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: chrX-111874665; COSMIC: COSV105290024;