rs17002034

Positions:

• chr22-40600363-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRTFA	NM_020831.6	c.-83-5628C>A		intron_variant		ENST00000355630.10	NP_065882.2
MRTFA	NM_001282661.3	c.-83-5628C>A		intron_variant			NP_001269590.2
MRTFA	NM_001282662.3	c.-83-5628C>A		intron_variant			NP_001269591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRTFA	ENST00000355630.10	c.-83-5628C>A		intron_variant		1	NM_020831.6	ENSP00000347847

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

Gnomad4 AFR AF: 0.0176

Gnomad4 AMR AF: 0.0804

Gnomad4 ASJ AF: 0.0617

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.0977

Gnomad4 OTH AF: 0.0705

Alfa AF: 0.0959 Hom.: 535

Bravo AF: 0.0736

Asia WGS AF: 0.170 AC: 590 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	2.9
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17002034; hg19: chr22-40996367;