22-40600363-G-T

Variant names:

• chr22-40600363-G-T
• rs17002034
• NM_020831.6:c.-83-5628C>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.-83-5628C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 152,188 control chromosomes in the GnomAD database, including 730 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 0.081 (730 hom., cov: 32)
• Consequence: MRTFA NM_020831.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 16 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 = 0.236 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020831.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRTFA	NM_020831.6	MANE Select	c.-83-5628C>A		intron	N/A	NP_065882.2
	MRTFA	NM_001282661.3		c.-83-5628C>A		intron	N/A	NP_001269590.2
	MRTFA	NM_001282662.3		c.-83-5628C>A		intron	N/A	NP_001269591.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRTFA	ENST00000355630.10	TSL:1 MANE Select	c.-83-5628C>A		intron	N/A	ENSP00000347847.5
	MRTFA	ENST00000402042.7	TSL:1	c.-83-5628C>A		intron	N/A	ENSP00000385584.3
	MRTFA	ENST00000463769.7	TSL:1	c.-22+36115C>A		intron	N/A	ENSP00000498788.2

Frequencies

GnomAD3 genomes AF: 0.0806 AC: 12256 AN: 152070 Hom.: 730 Cov.: 32

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0799

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0977

Gnomad OTH AF: 0.0722

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

GnomAD4 genome AF: 0.0805 AC: 12258 AN: 152188 Hom.: 730 Cov.: 32 AF XY: 0.0850 AC XY: 6323 AN XY: 74406

African (AFR) AF: 0.0176 AC: 730 AN: 41550

American (AMR) AF: 0.0804 AC: 1228 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0617 AC: 214 AN: 3470

East Asian (EAS) AF: 0.247 AC: 1278 AN: 5168

South Asian (SAS) AF: 0.118 AC: 570 AN: 4824

European-Finnish (FIN) AF: 0.124 AC: 1308 AN: 10572

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0977 AC: 6643 AN: 68004

Other (OTH) AF: 0.0705 AC: 149 AN: 2114

Alfa AF: 0.0894 Hom.: 976

Bravo AF: 0.0736

Asia WGS AF: 0.170 AC: 590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.55
PhyloP100		0.094
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: rs17002034; hg19: chr22-40996367;