Variant chr22-40411432-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_020831.6(MRTFA):c.3054C>T(p.Leu1018=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,582,260 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 2 hom. )

Consequence

MRTFA
NM_020831.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.95

Variant links:

Genes affected

MRTFA (HGNC:14334): (myocardin related transcription factor A) The protein encoded by this gene interacts with the transcription factor myocardin, a key regulator of smooth muscle cell differentiation. The encoded protein is predominantly nuclear and may help transduce signals from the cytoskeleton to the nucleus. This gene is involved in a specific translocation event that creates a fusion of this gene and the RNA-binding motif protein-15 gene. This translocation has been associated with acute megakaryocytic leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

MRTFA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 22-40411432-G-A is Benign according to our data. Variant chr22-40411432-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 720853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.95 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRTFA	NM_020831.6 linkuse as main transcript	c.3054C>T	p.Leu1018=	synonymous_variant	15/15	ENST00000355630.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRTFA	ENST00000355630.10 linkuse as main transcript	c.3054C>T	p.Leu1018=	synonymous_variant	15/15	1	NM_020831.6

Frequencies

GnomAD3 genomes

AF:

0.00138

AC:

210

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00251

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00137

AC:

331

AN:

241012

Hom.:

AF XY:

0.00140

AC XY:

182

AN XY:

130136

show subpopulations

Gnomad AFR exome

AF:

0.0000622

Gnomad AMR exome

AF:

0.000181

Gnomad ASJ exome

AF:

0.000226

Gnomad EAS exome

AF:

0.00181

Gnomad SAS exome

AF:

0.000902

Gnomad FIN exome

AF:

0.00124

Gnomad NFE exome

AF:

0.00209

Gnomad OTH exome

AF:

0.00155

GnomAD4 exome

AF:

0.00124

AC:

1768

AN:

1429972

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

893

AN XY:

705458

show subpopulations

Gnomad4 AFR exome

AF:

0.0000912

Gnomad4 AMR exome

AF:

0.000116

Gnomad4 ASJ exome

AF:

0.000564

Gnomad4 EAS exome

AF:

0.00480

Gnomad4 SAS exome

AF:

0.00102

Gnomad4 FIN exome

AF:

0.00157

Gnomad4 NFE exome

AF:

0.00120

Gnomad4 OTH exome

AF:

0.00133

GnomAD4 genome

AF:

0.00138

AC:

210

AN:

152288

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00213

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00251

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00223

Hom.:

Bravo

AF:

0.000884

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 25, 2021

- -

MRTFA-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 27, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.71

DANN

Benign

0.80

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

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