rs550921485
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_002143.3(HPCA):c.568G>A(p.Ala190Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000203 in 1,570,368 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 4 hom. )
Consequence
HPCA
NM_002143.3 missense
NM_002143.3 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 4.03
Genes affected
HPCA (HGNC:5144): (hippocalcin) The protein encoded by this gene is a member of neuron-specific calcium-binding proteins family found in the retina and brain. This protein is associated with the plasma membrane. It has similarities to proteins located in the photoreceptor cells that regulate photosignal transduction in a calcium-sensitive manner. This protein displays recoverin activity and a calcium-dependent inhibition of rhodopsin kinase. It is identical to the rat and mouse hippocalcin proteins and thought to play an important role in neurons of the central nervous system in a number of species. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.005412847).
BP6
?
Variant 1-32893848-G-A is Benign according to our data. Variant chr1-32893848-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 190120.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAdExome4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HPCA | NM_002143.3 | c.568G>A | p.Ala190Thr | missense_variant | 4/4 | ENST00000373467.4 | |
HPCA | XM_005270792.4 | c.568G>A | p.Ala190Thr | missense_variant | 4/4 | ||
HPCA | XM_017001118.3 | c.568G>A | p.Ala190Thr | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HPCA | ENST00000373467.4 | c.568G>A | p.Ala190Thr | missense_variant | 4/4 | 1 | NM_002143.3 | P1 | |
HPCA | ENST00000459874.5 | n.244G>A | non_coding_transcript_exon_variant | 3/3 | 2 | ||||
HPCA | ENST00000470166.5 | n.316G>A | non_coding_transcript_exon_variant | 3/3 | 2 | ||||
HPCA | ENST00000470896.1 | n.106+219G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152166Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000495 AC: 89AN: 179930Hom.: 3 AF XY: 0.000658 AC XY: 63AN XY: 95816
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GnomAD4 exome AF: 0.000214 AC: 303AN: 1418084Hom.: 4 Cov.: 31 AF XY: 0.000288 AC XY: 202AN XY: 701576
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GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74464
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ClinVar
Significance: Likely benign
Submissions summary: Pathogenic:1Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Torsion dystonia 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 02, 2015 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 07, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of helix (P = 0.0558);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at