NM_005159.5(ACTC1):c.129G>A (p.Gln43=) AND multiple conditions

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 10, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000228825.6

Allele description [Variation Report for NM_005159.5(ACTC1):c.129G>A (p.Gln43=)]

NM_005159.5(ACTC1):c.129G>A (p.Gln43=)

Genes:

GJD2-DT:GJD2 divergent transcript [Gene - HGNC]
ACTC1:actin alpha cardiac muscle 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q14

Genomic location:

Preferred name:

NM_005159.5(ACTC1):c.129G>A (p.Gln43=)

HGVS:

NC_000015.10:g.34794680C>T
NG_007553.1:g.6047G>A
NM_005159.5:c.129G>AMANE SELECT
NP_005150.1:p.Gln43=
LRG_388t1:c.129G>A
LRG_388:g.6047G>A
NC_000015.9:g.35086881C>T
NM_005159.4:c.129G>A

Links:

dbSNP: rs878854753

NCBI 1000 Genomes Browser:

rs878854753

Molecular consequence:

NM_005159.5:c.129G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Hypertrophic cardiomyopathy 11
Synonyms:: Familial hypertrophic cardiomyopathy 11; ACTC1-Related Familial Hypertrophic Cardiomyopathy
Identifiers:: MONDO: MONDO:0012799; MedGen: C2677506; OMIM: 612098

Name:: Dilated cardiomyopathy 1R (CMD1R)
Identifiers:: MONDO: MONDO:0013261; MedGen: C3150681; Orphanet: 154; Orphanet: 54260; OMIM: 613424

Name:: Atrial septal defect 5 (ASD5)
Identifiers:: MONDO: MONDO:0013011; MedGen: C2748552; Orphanet: 1478; OMIM: 612794

Recent activity

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selenophosphate synthetase [Brachyspira pilosicoli P43/6/78]
selenophosphate synthetase [Brachyspira pilosicoli P43/6/78]
gi|430781620|gnl|CORNELL|BPP43_0855 AGA66904.1|

Protein
Mus musculus cDNA, clone:Y0G0146N16, strand:minus, reference:ENSEMBL:Mouse-Trans...
Mus musculus cDNA, clone:Y0G0146N16, strand:minus, reference:ENSEMBL:Mouse-Transcript-ENST:ENSMUST00000034859, based on BLAT search
gi|56013077|dbj|AK188900.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000288803	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 10, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17576681, 9536098, 28492532
SCV002812099	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 1, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000288803

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 10, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002812099

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 1, 2021)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000288803.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change affects codon 43 of the ACTC1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ACTC1 protein. This variant also falls at the last nucleotide of exon 2, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with hypertrophic cardiomyopathy (Invitae). ClinVar contains an entry for this variant (Variation ID: 240098). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site.

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

From Fulgent Genetics, Fulgent Genetics, SCV002812099.1

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

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

Last Updated: May 1, 2024

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