chr5-78510059-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005779.3(LHFPL2):​c.155G>T​(p.Gly52Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,610,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: LHFPL2 NM_005779.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20165682).

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>T	p.Gly52Val	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>T	p.Gly52Val	missense	Exon 4 of 5	ENSP00000369702.2	Q6ZUX7
	LHFPL2	ENST00000515007.6	TSL:1	c.155G>T	p.Gly52Val	missense	Exon 2 of 3	ENSP00000425906.1	Q6ZUX7
	LHFPL2	ENST00000872133.1		c.155G>T	p.Gly52Val	missense	Exon 5 of 6	ENSP00000542192.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152196 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000981

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1457988 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 724968

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 44348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25992

East Asian (EAS) AF: 0.00 AC: 0 AN: 39606

South Asian (SAS) AF: 0.00 AC: 0 AN: 85894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1110426

Other (OTH) AF: 0.0000332 AC: 2 AN: 60200

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152196 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.00000833 AC: 1

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	Benign	0.071
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	13
DANN	Benign	0.30
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.5
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.25
Sift	Benign	0.47	T
Sift4G	Benign	0.31	T
Polyphen		0.0030	B
Vest4		0.48
MutPred		0.44		Loss of relative solvent accessibility (P = 0.0404)
MVP		0.41
MPC		0.55
ClinPred		0.11	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.11
gMVP		0.60
Mutation Taster		=81/19	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;