Genetic Variant HILPDA:p.Trp40Ser (chr7-128457387-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_013332.4(HILPDA):c.119G>C(p.Trp40Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

HILPDA
NM_013332.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.62

Variant links:

Genes affected

HILPDA (HGNC:28859): (hypoxia inducible lipid droplet associated) Enables signaling receptor binding activity. Involved in several processes, including autocrine signaling; cellular response to hypoxia; and positive regulation of lipid storage. Located in several cellular components, including cell surface; lipid droplet; and secretory granule. [provided by Alliance of Genome Resources, Apr 2022]

HILPDA links:

EFCAB3P1 (HGNC:56232): (EFCAB3 pseudogene 1)

EFCAB3P1 links:

ENSG00000273184 (HGNC:):

ENSG00000273184 links:

HILPDA-AS1 (HGNC:55641): (HILPDA antisense RNA 1)

HILPDA-AS1 links:

Genome browser will be placed here

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=0.11208162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HILPDA	NM_013332.4 link	c.119G>C	p.Trp40Ser	missense_variant	Exon 2 of 2	ENST00000257696.5	NP_037464.1	Q9Y5L2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HILPDA	ENST00000257696.5 link	c.119G>C	p.Trp40Ser	missense_variant	Exon 2 of 2	1	NM_013332.4	ENSP00000257696.4		Q9Y5L2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152134

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:

0.000386

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:

0.0000398

AC:

AN:

251466

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000489

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.119G>C (p.W40S) alteration is located in exon 2 (coding exon 1) of the HILPDA gene. This alteration results from a G to C substitution at nucleotide position 119, causing the tryptophan (W) at amino acid position 40 to be replaced by a serine (S). 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

0.15

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Benign

0.89

DEOGEN2

Benign

0.096

T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.45

.;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-12

D;D

REVEL

Benign

0.13

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.026

D;D

Polyphen

0.13

B;B

Vest4

0.41

MutPred

0.40

Gain of glycosylation at W40 (P = 0.0068);Gain of glycosylation at W40 (P = 0.0068);

MVP

0.072

MPC

0.83

ClinPred

0.57

GERP RS

3.9

Varity_R

0.86

gMVP

0.034

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