NM_005779.3:c.514T>C

Variant names:

• chr5-78489070-A-G
• NM_005779.3:c.514T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005779.3(LHFPL2):​c.514T>C​(p.Ser172Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 4.48
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.514T>C	p.Ser172Pro	missense	Exon 5 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.514T>C	p.Ser172Pro	missense	Exon 5 of 5	ENSP00000369702.2	Q6ZUX7
	LHFPL2	ENST00000515007.6	TSL:1	c.514T>C	p.Ser172Pro	missense	Exon 3 of 3	ENSP00000425906.1	Q6ZUX7
	LHFPL2	ENST00000872133.1		c.514T>C	p.Ser172Pro	missense	Exon 6 of 6	ENSP00000542192.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

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	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.68	D
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.5
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.42
Sift	Benign	0.12	T
Sift4G	Benign	0.20	T
Polyphen		0.90	P
Vest4		0.55
MutPred		0.49		Gain of methylation at K175 (P = 0.0727)
MVP		0.71
MPC		1.2
ClinPred		0.89	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.94
Mutation Taster		=65/35	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: chr5-77784893;