Variant chr22-40418496-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020831.6(MRTFA):c.2242A>G(p.Ser748Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,607,588 control chromosomes in the GnomAD database, including 145,842 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 23605 hom., cov: 32)

Exomes 𝑓: 0.40 ( 122237 hom. )

Consequence

MRTFA
NM_020831.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.06

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1725998E-6).

BP6

Variant 22-40418496-T-C is Benign according to our data. Variant chr22-40418496-T-C is described in ClinVar as [Benign]. Clinvar id is 1170078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRTFA	NM_020831.6 linkuse as main transcript	c.2242A>G	p.Ser748Gly	missense_variant	12/15	ENST00000355630.10	NP_065882.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRTFA	ENST00000355630.10 linkuse as main transcript	c.2242A>G	p.Ser748Gly	missense_variant	12/15	1	NM_020831.6	ENSP00000347847

Frequencies

GnomAD3 genomes

AF:

0.505

AC:

76609

AN:

151846

Hom.:

23537

Cov.:

show subpopulations

Gnomad AFR

AF:

0.866

Gnomad AMI

AF:

0.488

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.462

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.393

Gnomad OTH

AF:

0.454

GnomAD3 exomes

AF:

0.384

AC:

93123

AN:

242442

Hom.:

21434

AF XY:

0.387

AC XY:

50973

AN XY:

131676

show subpopulations

Gnomad AFR exome

AF:

0.879

Gnomad AMR exome

AF:

0.210

Gnomad ASJ exome

AF:

0.413

Gnomad EAS exome

AF:

0.109

Gnomad SAS exome

AF:

0.471

Gnomad FIN exome

AF:

0.325

Gnomad NFE exome

AF:

0.393

Gnomad OTH exome

AF:

0.388

GnomAD4 exome

AF:

0.398

AC:

578924

AN:

1455622

Hom.:

122237

Cov.:

AF XY:

0.399

AC XY:

288978

AN XY:

724332

show subpopulations

Gnomad4 AFR exome

AF:

0.891

Gnomad4 AMR exome

AF:

0.223

Gnomad4 ASJ exome

AF:

0.414

Gnomad4 EAS exome

AF:

0.137

Gnomad4 SAS exome

AF:

0.468

Gnomad4 FIN exome

AF:

0.329

Gnomad4 NFE exome

AF:

0.395

Gnomad4 OTH exome

AF:

0.412

GnomAD4 genome

AF:

0.505

AC:

76730

AN:

151966

Hom.:

23605

Cov.:

AF XY:

0.495

AC XY:

36727

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.867

Gnomad4 AMR

AF:

0.317

Gnomad4 ASJ

AF:

0.411

Gnomad4 EAS

AF:

0.118

Gnomad4 SAS

AF:

0.463

Gnomad4 FIN

AF:

0.323

Gnomad4 NFE

AF:

0.393

Gnomad4 OTH

AF:

0.457

Alfa

AF:

0.404

Hom.:

24055

Bravo

AF:

0.513

TwinsUK

AF:

0.371

AC:

1376

ALSPAC

AF:

0.383

AC:

1475

ESP6500AA

AF:

0.861

AC:

3792

ESP6500EA

AF:

0.397

AC:

3414

ExAC

AF:

0.396

AC:

48095

Asia WGS

AF:

0.363

AC:

1263

AN:

3476

EpiCase

AF:

0.409

EpiControl

AF:

0.405

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.0050

DANN

Benign

0.44

DEOGEN2

Benign

0.034

T;.;T;T;T;T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.041

.;T;T;T;T;T;T

MetaRNN

Benign

0.0000012

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

0.26

N;.;.;N;N;N;.

REVEL

Benign

0.077

Sift

Benign

0.41

T;.;.;T;T;T;.

Sift4G

Benign

0.51

T;T;T;T;T;T;T

Polyphen

0.0

B;.;.;B;B;B;.

Vest4

0.040

MPC

0.045

ClinPred

0.0086

GERP RS

-8.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.034

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