22-40526328-A-G

Position:

• chr22-40526328-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918

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

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MRTFA	NM_020831.6	c.241+25778T>C		intron_variant		ENST00000355630.10
MRTFA-AS1	NR_109965.1	n.1553A>G		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRTFA	ENST00000355630.10	c.241+25778T>C		intron_variant		1	NM_020831.6
MRTFA-AS1	ENST00000417123.1	n.1553A>G		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15356 AN: 152032 Hom.: 939 Cov.: 31

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: 3 AN: 36 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 2 AN XY: 24

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.0667

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.101 AC: 15390 AN: 152148 Hom.: 944 Cov.: 31 AF XY: 0.106 AC XY: 7895 AN XY: 74376

Gnomad4 AFR AF: 0.0664

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.0938

Alfa AF: 0.104 Hom.: 920

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
DANN	Benign	0.21

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

LitVar

Other links and lift over

dbSNP: rs5995871; hg19: chr22-40922332;