Genetic Variant LHFPL3:p.Met116Thr (chr7-104329126-T-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_199000.3(LHFPL3):c.347T>C(p.Met116Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000123 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

LHFPL3
NM_199000.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.92

Publications

0 publications found

Variant links:

Genes affected

LHFPL3 (HGNC:6589): (LHFPL tetraspan subfamily member 3) 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. A partial gene fragment named LHFPL4 corresponds to a portion of the first exon of this gene. [provided by RefSeq, Jul 2008]

LHFPL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.40605626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHFPL3	NM_199000.3 link	c.347T>C	p.Met116Thr	missense_variant	Exon 1 of 3	ENST00000424859.7	NP_945351.1	Q86UP9
LHFPL3	NM_001386065.1 link	c.347T>C	p.Met116Thr	missense_variant	Exon 1 of 4		NP_001372994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LHFPL3	ENST00000424859.7 link	c.347T>C	p.Met116Thr	missense_variant	Exon 1 of 3	1	NM_199000.3	ENSP00000393128.2	Q86UP9
LHFPL3	ENST00000401970.3 link	c.347T>C	p.Met116Thr	missense_variant	Exon 1 of 4	1		ENSP00000385374.3	A1L384
LHFPL3	ENST00000683240.1 link	n.264T>C		non_coding_transcript_exon_variant	Exon 1 of 4			ENSP00000508253.1	A0A804HL93

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000562

AC:

AN:

249218

AF XY:

0.0000444

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461710

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.000402

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111870

Other (OTH)

AF:

0.00

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.000187

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 04, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.347T>C (p.M116T) alteration is located in exon 1 (coding exon 1) of the LHFPL3 gene. This alteration results from a T to C substitution at nucleotide position 347, causing the methionine (M) at amino acid position 116 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

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.40

.;T

Eigen

Benign

-0.11

Eigen_PC

Benign

0.060

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.73

.;T

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.41

T;T

MetaSVM

Benign

-0.51

PhyloP100

4.9

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.8

D;D

REVEL

Uncertain

0.52

Sift

Benign

0.12

T;T

Sift4G

Benign

0.14

T;T

Vest4

0.59

MutPred

0.58

Loss of stability (P = 0.0755);Loss of stability (P = 0.0755);

MVP

0.39

ClinPred

0.25

GERP RS

5.1

gMVP

0.84

Mutation Taster

=6/94

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

7-104329126-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over