NM_020831.6:c.3054C>T

Variant names:

• chr22-40411432-G-A
• rs148865274
• NM_020831.6:c.3054C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_020831.6(MRTFA):​c.3054C>T​(p.Leu1018Leu) 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.95
• Publications: 2 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -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,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRTFA	NM_020831.6	c.3054C>T	p.Leu1018Leu	synonymous_variant	Exon 15 of 15	ENST00000355630.10	NP_065882.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRTFA	ENST00000355630.10	c.3054C>T	p.Leu1018Leu	synonymous_variant	Exon 15 of 15	1	NM_020831.6	ENSP00000347847.5

Frequencies

GnomAD3 genomes AF: 0.00138 AC: 210 AN: 152170 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.00137 AC: 331 AN: 241012 AF XY: 0.00140

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 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.: 2 Cov.: 31 AF XY: 0.00127 AC XY: 893 AN XY: 705458

African (AFR) AF: 0.0000912 AC: 3 AN: 32884

American (AMR) AF: 0.000116 AC: 5 AN: 42996

Ashkenazi Jewish (ASJ) AF: 0.000564 AC: 14 AN: 24832

East Asian (EAS) AF: 0.00480 AC: 187 AN: 38940

South Asian (SAS) AF: 0.00102 AC: 86 AN: 84046

European-Finnish (FIN) AF: 0.00157 AC: 83 AN: 52798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5648

European-Non Finnish (NFE) AF: 0.00120 AC: 1312 AN: 1089002

Other (OTH) AF: 0.00133 AC: 78 AN: 58826

GnomAD4 genome AF: 0.00138 AC: 210 AN: 152288 Hom.: 0 Cov.: 32 AF XY: 0.00124 AC XY: 92 AN XY: 74472

African (AFR) AF: 0.0000962 AC: 4 AN: 41562

American (AMR) AF: 0.000131 AC: 2 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5174

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4826

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00251 AC: 171 AN: 68028

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00223 Hom.: 1

Bravo AF: 0.000884

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MRTFA: BP4, BP7 -

not specified Benign:1

May 25, 2021

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

MRTFA-related disorder Benign:1

Mar 27, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.71
DANN	Benign	0.80
PhyloP100		-2.0
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs148865274; hg19: chr22-40807436;