NM_020831.6:c.-22+18131G>A

Variant names:

• chr22-40576543-C-T
• rs1022533
• NM_020831.6:c.-22+18131G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020831.6(MRTFA):​c.-22+18131G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,890 control chromosomes in the GnomAD database, including 8,352 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 0.32 (8352 hom., cov: 30)
• Consequence: MRTFA NM_020831.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRTFA	NM_020831.6	c.-22+18131G>A		intron_variant	Intron 2 of 14	ENST00000355630.10	NP_065882.2
MRTFA	NM_001282661.3	c.-22+18131G>A		intron_variant	Intron 2 of 13		NP_001269590.2
MRTFA	NM_001282662.3	c.-22+18131G>A		intron_variant	Intron 2 of 14		NP_001269591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRTFA	ENST00000355630.10	c.-22+18131G>A		intron_variant	Intron 2 of 14	1	NM_020831.6	ENSP00000347847.5

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48697 AN: 151772 Hom.: 8356 Cov.: 30

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.343

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.321 AC: 48699 AN: 151890 Hom.: 8352 Cov.: 30 AF XY: 0.319 AC XY: 23683 AN XY: 74238

African (AFR) AF: 0.245 AC: 10159 AN: 41408

American (AMR) AF: 0.283 AC: 4319 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1331 AN: 3466

East Asian (EAS) AF: 0.626 AC: 3229 AN: 5160

South Asian (SAS) AF: 0.236 AC: 1136 AN: 4816

European-Finnish (FIN) AF: 0.337 AC: 3551 AN: 10544

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23867 AN: 67944

Other (OTH) AF: 0.341 AC: 721 AN: 2112

Alfa AF: 0.329 Hom.: 7484

Bravo AF: 0.317

Asia WGS AF: 0.347 AC: 1204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.74
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1022533; hg19: chr22-40972547;