1-39684142-T-C

Variant names:

• chr1-39684142-T-C
• rs1646652133
• NM_016257.4:c.173A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016257.4(HPCAL4):​c.173A>G​(p.Tyr58Cys) variant causes a missense change involving the alteration of a 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: 33)
• Consequence: HPCAL4 NM_016257.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.90
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.772

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPCAL4	NM_016257.4	MANE Select	c.173A>G	p.Tyr58Cys	missense	Exon 3 of 4	NP_057341.1	Q9UM19
	HPCAL4	NM_001282396.2		c.173A>G	p.Tyr58Cys	missense	Exon 4 of 5	NP_001269325.1	Q9UM19
	HPCAL4	NM_001282397.2		c.162+300A>G		intron	N/A	NP_001269326.1	B4DGW9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPCAL4	ENST00000372844.8	TSL:1 MANE Select	c.173A>G	p.Tyr58Cys	missense	Exon 3 of 4	ENSP00000361935.3	Q9UM19
	HPCAL4	ENST00000617690.2	TSL:5	c.173A>G	p.Tyr58Cys	missense	Exon 4 of 5	ENSP00000481834.1	Q9UM19
	HPCAL4	ENST00000945844.1		c.173A>G	p.Tyr58Cys	missense	Exon 4 of 5	ENSP00000615903.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.075	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.8	L
PhyloP100		7.9
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-6.4	D
REVEL	Uncertain	0.38
Sift	Benign	0.042	D
Sift4G	Benign	0.17	T
Polyphen		0.99	D
Vest4		0.81
MutPred		0.39		Gain of catalytic residue at P57 (P = 0.0103)
MVP		0.61
MPC		1.8
ClinPred		0.99	D
GERP RS		3.5
Varity_R		0.47
gMVP		0.75
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1646652133; hg19: chr1-40149814;