Genetic Variant MRTFA:c.241+25778T>C (chr22-40526328-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020831.6(MRTFA):c.241+25778T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,184 control chromosomes in the GnomAD database, including 944 homozygotes. 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 0.10 ( 944 hom., cov: 31)

Exomes 𝑓: 0.083 ( 0 hom. )

Consequence

MRTFA
NM_020831.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.918

Publications

9 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 links:

MRTFA-AS1 (HGNC:40681): (MRTFA antisense RNA 1)

MRTFA-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.07).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRTFA	NM_020831.6 link	c.241+25778T>C		intron_variant	Intron 3 of 14	ENST00000355630.10	NP_065882.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRTFA	ENST00000355630.10 link	c.241+25778T>C		intron_variant	Intron 3 of 14	1	NM_020831.6	ENSP00000347847.5

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15356

AN:

152032

Hom.:

939

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0656

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.0963

GnomAD4 exome

AF:

0.0833

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0833

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0667

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

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

GnomAD4 genome

AF:

0.101

AC:

15390

AN:

152148

Hom.:

944

Cov.:

AF XY:

0.106

AC XY:

7895

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0664

AC:

2756

AN:

41532

American (AMR)

AF:

0.102

AC:

1563

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

446

AN:

3470

East Asian (EAS)

AF:

0.248

AC:

1282

AN:

5170

South Asian (SAS)

AF:

0.122

AC:

588

AN:

4812

European-Finnish (FIN)

AF:

0.125

AC:

1319

AN:

10586

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.104

AC:

7068

AN:

67998

Other (OTH)

AF:

0.0938

AC:

198

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

692

1384

2076

2768

3460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.103

Hom.:

1289

Bravo

AF:

0.0954

Asia WGS

AF:

0.184

AC:

640

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.26

(source)

DANN

Benign

0.21

PhyloP100

-0.92

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over