NM_005779.3:c.94G>C

Variant names:

• chr5-78510120-C-G
• NM_005779.3:c.94G>C

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005779.3. 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
	LHFPL2	NM_005779.3	MANE Select	c.94G>C	p.Asp32His	missense	Exon 4 of 5	NP_005770.1	Q6ZUX7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHFPL2	ENST00000380345.7	TSL:5 MANE Select	c.94G>C	p.Asp32His	missense	Exon 4 of 5	ENSP00000369702.2	Q6ZUX7
	LHFPL2	ENST00000515007.6	TSL:1	c.94G>C	p.Asp32His	missense	Exon 2 of 3	ENSP00000425906.1	Q6ZUX7
	LHFPL2	ENST00000872133.1		c.94G>C	p.Asp32His	missense	Exon 5 of 6	ENSP00000542192.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	0.53
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	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
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.8	L
PhyloP100		7.5
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.34	N
REVEL	Uncertain	0.42
Sift	Benign	0.16	T
Sift4G	Benign	0.28	T
Polyphen		1.0	D
Vest4		0.79
MutPred		0.63		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
Mutation Taster		=53/47	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

hg19: chr5-77805943;