Variant chr3-14125052-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_024334.3(TMEM43):c.-142G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,070,850 control chromosomes in the GnomAD database, including 640 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 101 hom., cov: 33)

Exomes 𝑓: 0.011 ( 539 hom. )

Consequence

TMEM43
NM_024334.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.223

Variant links:

Genes affected

TMEM43 (HGNC:28472): (transmembrane protein 43) This gene belongs to the TMEM43 family. Defects in this gene are the cause of familial arrhythmogenic right ventricular dysplasia type 5 (ARVD5), also known as arrhythmogenic right ventricular cardiomyopathy type 5 (ARVC5). Arrhythmogenic right ventricular dysplasia is an inherited disorder, often involving both ventricles, and is characterized by ventricular tachycardia, heart failure, sudden cardiac death, and fibrofatty replacement of cardiomyocytes. This gene contains a response element for PPAR gamma (an adipogenic transcription factor), which may explain the fibrofatty replacement of the myocardium, a characteristic pathological finding in ARVC. [provided by RefSeq, Oct 2008]

TMEM43 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 3-14125052-G-A is Benign according to our data. Variant chr3-14125052-G-A is described in ClinVar as [Benign]. Clinvar id is 1276969.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM43	NM_024334.3 linkuse as main transcript	c.-142G>A		5_prime_UTR_variant	1/12	ENST00000306077.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM43	ENST00000306077.5 linkuse as main transcript	c.-142G>A		5_prime_UTR_variant	1/12	1	NM_024334.3	P1
TMEM43	ENST00000432444.2 linkuse as main transcript	c.-142G>A		5_prime_UTR_variant, NMD_transcript_variant	1/13	3

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

2087

AN:

152240

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0570

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.0279

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.0143

GnomAD4 exome

AF:

0.0107

AC:

9845

AN:

918492

Hom.:

539

Cov.:

AF XY:

0.00990

AC XY:

4674

AN XY:

472114

show subpopulations

Gnomad4 AFR exome

AF:

0.000880

Gnomad4 AMR exome

AF:

0.0859

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.143

Gnomad4 SAS exome

AF:

0.00174

Gnomad4 FIN exome

AF:

0.0256

Gnomad4 NFE exome

AF:

0.000540

Gnomad4 OTH exome

AF:

0.0116

GnomAD4 genome

AF:

0.0137

AC:

2094

AN:

152358

Hom.:

101

Cov.:

AF XY:

0.0160

AC XY:

1191

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00164

Gnomad4 AMR

AF:

0.0575

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.00310

Gnomad4 FIN

AF:

0.0279

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.0172

Asia WGS

AF:

0.0440

AC:

152

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.6

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over