Variant 2-10419914-G-A 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_002149.4(HPCAL1):c.157G>A(p.Ala53Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,613,674 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: 𝑓 0.00019 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

HPCAL1
NM_002149.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.93

Variant links:

Genes affected

HPCAL1 (HGNC:5145): (hippocalcin like 1) The protein encoded by this gene is a member of neuron-specific calcium-binding proteins family found in the retina and brain. It is highly similar to human hippocalcin protein and nearly identical to the rat and mouse hippocalcin like-1 proteins. It may be involved in the calcium-dependent regulation of rhodopsin phosphorylation and may be of relevance for neuronal signalling in the central nervous system. Several alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Apr 2012]

HPCAL1 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=0.22137123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPCAL1	NM_002149.4 linkuse as main transcript	c.157G>A	p.Ala53Thr	missense_variant	3/5	ENST00000307845.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPCAL1	ENST00000307845.8 linkuse as main transcript	c.157G>A	p.Ala53Thr	missense_variant	3/5	1	NM_002149.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

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:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000637

AC:

AN:

251102

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000882

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000151

AC:

220

AN:

1461574

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

108

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000174

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000191

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.000721

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000494

Hom.:

Bravo

AF:

0.000314

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

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

Jul 13, 2022

The c.157G>A (p.A53T) alteration is located in exon 4 (coding exon 1) of the HPCAL1 gene. This alteration results from a G to A substitution at nucleotide position 157, causing the alanine (A) at amino acid position 53 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

0.25

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.34

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.076

T;T;T;T;T

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.021

MetaRNN

Benign

0.22

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.98

L;L;L;L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.2

N;N;.;.;.

REVEL

Benign

0.23

Sift

Benign

0.24

T;T;.;.;.

Sift4G

Benign

0.49

T;T;T;T;T

Polyphen

0.52

P;P;P;P;P

Vest4

0.52

MVP

0.24

MPC

1.3

ClinPred

0.074

GERP RS

5.2

Varity_R

0.22

gMVP

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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