Genetic Variant NM_005159.5:c.*137A>C (chr15-34790275-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005159.5(ACTC1):c.*137A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000043 in 1,162,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000040 ( 0 hom. )

Consequence

ACTC1
NM_005159.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.10

Publications

0 publications found

Variant links:

Genes affected

ACTC1 (HGNC:143): (actin alpha cardiac muscle 1) Actins are highly conserved proteins that are involved in various types of cell motility. Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to four others. The protein encoded by this gene belongs to the actin family which is comprised of three main groups of actin isoforms, alpha, beta, and gamma. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. Defects in this gene have been associated with idiopathic dilated cardiomyopathy (IDC) and familial hypertrophic cardiomyopathy (FHC). [provided by RefSeq, Jul 2008]

ACTC1 links:

GJD2-DT (HGNC:55560): (GJD2 divergent transcript)

GJD2-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005159.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACTC1	NM_005159.5	MANE Select	c.*137A>C	3_prime_UTR	Exon 7 of 7	NP_005150.1	P68032
ACTC1	NM_001406482.1		c.*137A>C	3_prime_UTR	Exon 6 of 6	NP_001393411.1	P68032
ACTC1	NM_001406483.1		c.*137A>C	3_prime_UTR	Exon 7 of 7	NP_001393412.1	P68032

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACTC1	ENST00000290378.6	TSL:1 MANE Select	c.*137A>C	3_prime_UTR	Exon 7 of 7	ENSP00000290378.4	P68032
ACTC1	ENST00000713613.1		c.*137A>C	3_prime_UTR	Exon 8 of 8	ENSP00000518909.1	A0AAQ5BGG2
ACTC1	ENST00000868408.1		c.*137A>C	3_prime_UTR	Exon 7 of 7	ENSP00000538467.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000396

AC:

AN:

1010106

Hom.:

Cov.:

AF XY:

0.00000386

AC XY:

AN XY:

518618

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24352

American (AMR)

AF:

0.00

AC:

AN:

40596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22662

East Asian (EAS)

AF:

0.00

AC:

AN:

36474

South Asian (SAS)

AF:

0.00

AC:

AN:

74952

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49780

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3222

European-Non Finnish (NFE)

AF:

0.00000561

AC:

AN:

712954

Other (OTH)

AF:

0.00

AC:

AN:

45114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41434

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

2.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over