5-78510120-C-G

Position:

• chr5-78510120-C-G

Variant summary

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

The NM_005779.3(LHFPL2):​c.94G>C​(p.Asp32His) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 33)
• Consequence: LHFPL2 NM_005779.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.46

Genes affected

LHFPL2 (HGNC:6588): (LHFPL tetraspan subfamily member 2) 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.802

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LHFPL2	NM_005779.3	c.94G>C	p.Asp32His	missense_variant	4/5	ENST00000380345.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHFPL2	ENST00000380345.7	c.94G>C	p.Asp32His	missense_variant	4/5	5	NM_005779.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Jul 14, 2023

The c.94G>C (p.D32H) alteration is located in exon 4 (coding exon 1) of the LHFPL2 gene. This alteration results from a G to C substitution at nucleotide position 94, causing the aspartic acid (D) at amino acid position 32 to be replaced by a histidine (H). 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	0.53
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	.;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.34	N;N
REVEL	Uncertain	0.42
Sift	Benign	0.16	T;T
Sift4G	Benign	0.28	T;T
Polyphen		1.0	D;D
Vest4		0.79
MutPred		0.63		Loss of stability (P = 0.0223);Loss of stability (P = 0.0223);
MVP		0.85
MPC		0.57
ClinPred		0.92	D
GERP RS		5.0
Varity_R		0.68
gMVP		0.90

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: chr5-77805943;