13-39343998-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005780.3(LHFPL6):ā€‹c.541A>Gā€‹(p.Met181Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,680 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000055 ( 0 hom. )

Consequence

LHFPL6
NM_005780.3 missense

Scores

9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.86
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LHFPL6NM_005780.3 linkuse as main transcriptc.541A>G p.Met181Val missense_variant 4/4 ENST00000379589.4 NP_005771.1 Q9Y693A0A024RDR1
LHFPL6XM_011534861.2 linkuse as main transcriptc.541A>G p.Met181Val missense_variant 4/4 XP_011533163.1 Q9Y693A0A024RDR1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LHFPL6ENST00000379589.4 linkuse as main transcriptc.541A>G p.Met181Val missense_variant 4/41 NM_005780.3 ENSP00000368908.3 Q9Y693
LHFPL6ENST00000648377.1 linkuse as main transcriptn.541A>G non_coding_transcript_exon_variant 4/14 ENSP00000496801.1 Q9Y693

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152104
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250906
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135626
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000466
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461576
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
727068
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152104
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000416
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsDec 02, 2024The c.541A>G (p.M181V) alteration is located in exon 4 (coding exon 3) of the LHFP gene. This alteration results from a A to G substitution at nucleotide position 541, causing the methionine (M) at amino acid position 181 to be replaced by a valine (V). 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
0.11
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.25
T
Eigen
Benign
0.073
Eigen_PC
Benign
0.15
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.046
D
MetaRNN
Uncertain
0.69
D
MetaSVM
Benign
-0.72
T
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.77
N
REVEL
Uncertain
0.47
Sift
Uncertain
0.021
D
Sift4G
Benign
0.43
T
Polyphen
0.45
P
Vest4
0.58
MutPred
0.86
Gain of catalytic residue at M181 (P = 0.2095);
MVP
0.55
MPC
0.36
ClinPred
0.52
D
GERP RS
4.0
Varity_R
0.13
gMVP
0.71

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.

Other links and lift over

dbSNP: rs764491779; hg19: chr13-39918135; COSMIC: COSV65444396; API