X-112671126-C-T

Position:

• chrX-112671126-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_178175.4(LHFPL1):​c.265G>A​(p.Gly89Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: LHFPL1 NM_178175.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.86

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]

LHFPL1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.782

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHFPL1	NM_178175.4	c.265G>A	p.Gly89Ser	missense_variant	2/4	ENST00000371968.8	NP_835469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHFPL1	ENST00000371968.8	c.265G>A	p.Gly89Ser	missense_variant	2/4	1	NM_178175.4	ENSP00000361036.3
LHFPL1	ENST00000478229.1	n.226+8703G>A		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 18, 2024

The c.265G>A (p.G89S) alteration is located in exon 2 (coding exon 1) of the LHFPL1 gene. This alteration results from a G to A substitution at nucleotide position 265, causing the glycine (G) at amino acid position 89 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	D
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.33	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.1	L
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.41
Sift	Benign	0.13	T
Sift4G	Benign	0.074	T
Polyphen		0.34	B
Vest4		0.55
MutPred		0.77		Gain of glycosylation at G89 (P = 0.0812);
MVP		0.71
MPC		0.49
ClinPred		0.97	D
GERP RS		5.3
Varity_R		0.52
gMVP		0.79

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-111914354;