Genetic Variant NM_016257.4:c.567G>A (chr1-39682545-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016257.4(HPCAL4):c.567G>A(p.Met189Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HPCAL4
NM_016257.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.87

Publications

0 publications found

Variant links:

Genes affected

HPCAL4 (HGNC:18212): (hippocalcin like 4) The protein encoded by this gene is highly similar to human hippocalcin protein and hippocalcin like-1 protein. It also has similarity to rat neural visinin-like Ca2+-binding protein-type 1 and 2 proteins. This encoded protein may be involved in the calcium-dependent regulation of rhodopsin phosphorylation. The transcript of this gene has multiple polyadenylation sites. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

HPCAL4 links:

ENSG00000293757 (HGNC:):

ENSG00000293757 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.118952304).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016257.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HPCAL4	NM_016257.4	MANE Select	c.567G>A	p.Met189Ile	missense	Exon 4 of 4	NP_057341.1	Q9UM19
HPCAL4	NM_001282396.2		c.567G>A	p.Met189Ile	missense	Exon 5 of 5	NP_001269325.1	Q9UM19
HPCAL4	NM_001282397.2		c.351G>A	p.Met117Ile	missense	Exon 3 of 3	NP_001269326.1	B4DGW9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HPCAL4	ENST00000372844.8	TSL:1 MANE Select	c.567G>A	p.Met189Ile	missense	Exon 4 of 4	ENSP00000361935.3	Q9UM19
HPCAL4	ENST00000617690.2	TSL:5	c.567G>A	p.Met189Ile	missense	Exon 5 of 5	ENSP00000481834.1	Q9UM19
HPCAL4	ENST00000945844.1		c.567G>A	p.Met189Ile	missense	Exon 5 of 5	ENSP00000615903.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251482

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727238

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:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112000

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.034

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.057

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.79

M_CAP

Benign

0.016

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.13

PhyloP100

3.9

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.42

REVEL

Uncertain

0.30

Sift

Benign

1.0

Sift4G

Benign

0.73

Polyphen

0.0

Vest4

0.27

MutPred

0.26

Gain of helix (P = 0.0325)

MVP

0.65

MPC

0.68

ClinPred

0.75

GERP RS

4.3

Varity_R

0.36

gMVP

0.67

Mutation Taster

=76/24

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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