Variant chr2-10419893-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.136G>A(p.Asp46Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,618 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: 31)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

HPCAL1
NM_002149.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

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:

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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=0.261971).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPCAL1	NM_002149.4 linkuse as main transcript	c.136G>A	p.Asp46Asn	missense_variant	3/5	ENST00000307845.8	NP_002140.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPCAL1	ENST00000307845.8 linkuse as main transcript	c.136G>A	p.Asp46Asn	missense_variant	3/5	1	NM_002149.4	ENSP00000310749	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251026

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135844

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:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461618

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

The c.136G>A (p.D46N) 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 136, causing the aspartic acid (D) at amino acid position 46 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T;T;T;T

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

.;.;.;D;.

M_CAP

Benign

0.070

MetaRNN

Benign

0.26

T;T;T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.7

L;L;L;L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.5

D;D;.;.;.

REVEL

Benign

0.18

Sift

Benign

0.080

T;T;.;.;.

Sift4G

Benign

0.20

T;T;T;T;T

Polyphen

0.015

B;B;B;B;B

Vest4

0.24

MutPred

0.37

Gain of methylation at K49 (P = 0.0805);Gain of methylation at K49 (P = 0.0805);Gain of methylation at K49 (P = 0.0805);Gain of methylation at K49 (P = 0.0805);Gain of methylation at K49 (P = 0.0805);

MVP

0.63

MPC

1.8

ClinPred

0.95

GERP RS

5.2

Varity_R

0.30

gMVP

0.77

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