Genetic Variant HILPDA:p.Thr52Ala (chr7-128457422-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_013332.4(HILPDA):c.154A>G(p.Thr52Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T52P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HILPDA
NM_013332.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0580

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044889748).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013332.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HILPDA	NM_013332.4	MANE Select	c.154A>G	p.Thr52Ala	missense	Exon 2 of 2	NP_037464.1	Q9Y5L2
HILPDA	NM_001098786.2		c.154A>G	p.Thr52Ala	missense	Exon 2 of 2	NP_001092256.1	Q9Y5L2
EFCAB3P1	NR_190220.1		n.368A>G		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HILPDA	ENST00000257696.5	TSL:1 MANE Select	c.154A>G	p.Thr52Ala	missense	Exon 2 of 2	ENSP00000257696.4	Q9Y5L2
HILPDA	ENST00000435296.2	TSL:2	c.154A>G	p.Thr52Ala	missense	Exon 2 of 2	ENSP00000388871.2	Q9Y5L2
HILPDA	ENST00000916177.1		c.154A>G	p.Thr52Ala	missense	Exon 2 of 2	ENSP00000586236.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

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:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112004

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.3

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.018

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.29

M_CAP

Benign

0.0019

MetaRNN

Benign

0.045

MetaSVM

Benign

-1.0

PhyloP100

-0.058

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.58

REVEL

Benign

0.034

Sift

Benign

0.22

Sift4G

Benign

0.22

Polyphen

0.0

Vest4

0.041

MutPred

0.069

Loss of phosphorylation at T52 (P = 0.015)

MVP

0.014

MPC

0.16

ClinPred

0.016

GERP RS

0.85

Varity_R

0.080

gMVP

0.0094

Mutation Taster

=99/1

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over