Variant 13-39600910-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005780.3(LHFPL6):c.307G>A(p.Ala103Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000877 in 1,585,186 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000094 ( 1 hom. )

Consequence

LHFPL6
NM_005780.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.83

Variant links:

Genes affected

LHFPL6 (HGNC:6586): (LHFPL tetraspan subfamily member 6) 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. This gene is fused to a high-mobility group gene in a translocation-associated lipoma. Mutations in another LHFP-like gene result in deafness in humans and mice. Alternatively spliced transcript variants have been found; however, their full-length nature is not known. [provided by RefSeq, Jul 2008]

LHFPL6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19788298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LHFPL6	NM_005780.3 linkuse as main transcript	c.307G>A	p.Ala103Thr	missense_variant	2/4	ENST00000379589.4
LHFPL6	XM_011534861.2 linkuse as main transcript	c.307G>A	p.Ala103Thr	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHFPL6	ENST00000379589.4 linkuse as main transcript	c.307G>A	p.Ala103Thr	missense_variant	2/4	1	NM_005780.3	P1
LHFPL6	ENST00000648377.1 linkuse as main transcript	c.307G>A	p.Ala103Thr	missense_variant, NMD_transcript_variant	2/14

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

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:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000181

AC:

AN:

231948

Hom.:

AF XY:

0.000218

AC XY:

AN XY:

124134

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000549

Gnomad SAS exome

AF:

0.00120

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000855

Gnomad OTH exome

AF:

0.000180

GnomAD4 exome

AF:

0.0000935

AC:

134

AN:

1433010

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

709088

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00103

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000365

Gnomad4 OTH exome

AF:

0.0000847

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000486

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.000231

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

The c.307G>A (p.A103T) alteration is located in exon 2 (coding exon 1) of the LHFP gene. This alteration results from a G to A substitution at nucleotide position 307, causing the alanine (A) at amino acid position 103 to be replaced by a threonine (T). 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

Benign

0.30

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.38

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.085

MetaRNN

Benign

0.20

MetaSVM

Uncertain

0.17

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-2.0

REVEL

Uncertain

0.42

Sift

Benign

0.070

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.46

MVP

0.68

MPC

0.85

ClinPred

0.27

GERP RS

5.4

Varity_R

0.21

gMVP

0.84

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over