22-40418496-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S748R) has been classified as Uncertain significance.

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

Publications

34 publications found

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 Gene-Disease associations (from GenCC):

immunodeficiency 66
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

MRTFA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MRTFA	NM_020831.6 link	c.2242A>G	p.Ser748Gly	missense_variant	Exon 12 of 15	ENST00000355630.10	NP_065882.2	Q969V6A4FUJ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRTFA	ENST00000355630.10 link	c.2242A>G	p.Ser748Gly	missense_variant	Exon 12 of 15	1	NM_020831.6	ENSP00000347847.5		A0A499FIJ6

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

GnomAD2 exomes

AF:

0.384

AC:

93123

AN:

242442

AF XY:

0.387

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 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

African (AFR)

AF:

0.891

AC:

29688

AN:

33308

American (AMR)

AF:

0.223

AC:

9460

AN:

42346

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

10604

AN:

25640

East Asian (EAS)

AF:

0.137

AC:

5421

AN:

39684

South Asian (SAS)

AF:

0.468

AC:

40071

AN:

85666

European-Finnish (FIN)

AF:

0.329

AC:

17536

AN:

53244

Middle Eastern (MID)

AF:

0.486

AC:

2784

AN:

5730

European-Non Finnish (NFE)

AF:

0.395

AC:

438608

AN:

1109894

Other (OTH)

AF:

0.412

AC:

24752

AN:

60110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

21967

43935

65902

87870

109837

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.505

AC:

76730

AN:

151966

Hom.:

23605

Cov.:

AF XY:

0.495

AC XY:

36727

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.867

AC:

35957

AN:

41496

American (AMR)

AF:

0.317

AC:

4843

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.411

AC:

1425

AN:

3470

East Asian (EAS)

AF:

0.118

AC:

603

AN:

5126

South Asian (SAS)

AF:

0.463

AC:

2229

AN:

4810

European-Finnish (FIN)

AF:

0.323

AC:

3420

AN:

10578

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.393

AC:

26689

AN:

67884

Other (OTH)

AF:

0.457

AC:

966

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1575

3150

4725

6300

7875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.427

Hom.:

41190

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

-2.1

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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.

22-40418496-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over