NM_005477.3(HCN4):c.3582A>G (p.Pro1194=) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 15, 2017
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000579016.1

Allele description [Variation Report for NM_005477.3(HCN4):c.3582A>G (p.Pro1194=)]

NM_005477.3(HCN4):c.3582A>G (p.Pro1194=)

Gene:

HCN4:hyperpolarization activated cyclic nucleotide gated potassium channel 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q24.1

Genomic location:

Preferred name:

NM_005477.3(HCN4):c.3582A>G (p.Pro1194=)

HGVS:

NC_000015.10:g.73322511T>C
NG_009063.1:g.51754A>G
NM_005477.3:c.3582A>GMANE SELECT
NP_005468.1:p.Pro1194=
NC_000015.9:g.73614852T>C
NM_005477.2:c.3582A>G

Links:

dbSNP: rs375637572

NCBI 1000 Genomes Browser:

rs375637572

Molecular consequence:

NM_005477.3:c.3582A>G - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000681261	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Dec 15, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000681261

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Dec 15, 2017)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000681261.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

A variant of uncertain significance has been identified in the HCN4 gene. The c.3582 A>G variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 8/32542 (0.025%) alleles from individuals of Latino ancestry in large population cohorts (Lek et al., 2016). The c.3582 A>G variant results in a synonymous change of the P1194 residue in the HCN4 gene. Although this substitution occurs at a position that is not conserved across species, and guanine (G) is the wild type nucleotide in multiple species, in silico splice prediction algorithms suggest that this variant may create a cryptic splice donor site, upstream of the natural splice donor site, leading to abnormal splicing in the HCN4 gene. However, in the absence of functional mRNA studies, the physiological consequence of this variant cannot be precisely determined.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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