5-78510059-C-T

Variant names:

• chr5-78510059-C-T
• rs751701207
• NM_005779.3:c.155G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005779.3(LHFPL2):​c.155G>A​(p.Gly52Asp) 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. 17/22 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. G52V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LHFPL2 NM_005779.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.46
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3170402).

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.155G>A	p.Gly52Asp	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.155G>A	p.Gly52Asp	missense	Exon 4 of 5	ENSP00000369702.2	Q6ZUX7
	LHFPL2	ENST00000515007.6	TSL:1	c.155G>A	p.Gly52Asp	missense	Exon 2 of 3	ENSP00000425906.1	Q6ZUX7
	LHFPL2	ENST00000872133.1		c.155G>A	p.Gly52Asp	missense	Exon 5 of 6	ENSP00000542192.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000430 AC: 1 AN: 232494 AF XY: 0.00000783

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000578

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	13
DANN	Benign	0.39
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.5
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.20
Sift	Benign	0.65	T
Sift4G	Benign	0.88	T
Polyphen		0.17	B
Vest4		0.55
MutPred		0.40		Loss of catalytic residue at S53 (P = 0.0359)
MVP		0.37
MPC		0.67
ClinPred		0.19	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.084
gMVP		0.60
Mutation Taster		=83/17	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

dbSNP: rs751701207; hg19: chr5-77805882;