1-32889063-C-A

Position:

• chr1-32889063-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002143.3(HPCA):​c.165C>A​(p.Phe55Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HPCA NM_002143.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.37

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.746

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPCA	NM_002143.3	c.165C>A	p.Phe55Leu	missense_variant	2/4	ENST00000373467.4
HPCA	XM_005270792.4	c.165C>A	p.Phe55Leu	missense_variant	2/4
HPCA	XM_017001118.3	c.165C>A	p.Phe55Leu	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPCA	ENST00000373467.4	c.165C>A	p.Phe55Leu	missense_variant	2/4	1	NM_002143.3	P1
HPCA	ENST00000480118.5	n.224C>A		non_coding_transcript_exon_variant	2/3	5
HPCA	ENST00000459874.5	n.54+2548C>A		intron_variant, non_coding_transcript_variant		2
HPCA	ENST00000470166.5	n.126+2944C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	D
Eigen	Benign	0.0046
Eigen_PC	Benign	0.099
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.071	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.056	T
Polyphen		0.036	B
Vest4		0.80
MutPred		0.78		Loss of catalytic residue at F55 (P = 0.0823);
MVP		0.28
MPC		1.1
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.83
gMVP		0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-33354664;