NM_020831.6:c.241+25778T>C

Variant names:

• chr22-40526328-A-G
• rs5995871
• NM_020831.6:c.241+25778T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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-AS1 (HGNC:40681): (MRTFA antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

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.241+25778T>C		intron	N/A	NP_065882.2
	MRTFA-AS1	NR_109965.1		n.1553A>G		non_coding_transcript_exon	Exon 4 of 4
	MRTFA	NM_001282661.3		c.241+25778T>C		intron	N/A	NP_001269590.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRTFA	ENST00000355630.10	TSL:1 MANE Select	c.241+25778T>C		intron	N/A	ENSP00000347847.5
	MRTFA	ENST00000402042.7	TSL:1	c.241+25778T>C		intron	N/A	ENSP00000385584.3
	MRTFA	ENST00000463769.7	TSL:1	c.241+25778T>C		intron	N/A	ENSP00000498788.2

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0667 AC: 2 AN: 30

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.0664 AC: 2756 AN: 41532

American (AMR) AF: 0.102 AC: 1563 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 446 AN: 3470

East Asian (EAS) AF: 0.248 AC: 1282 AN: 5170

South Asian (SAS) AF: 0.122 AC: 588 AN: 4812

European-Finnish (FIN) AF: 0.125 AC: 1319 AN: 10586

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7068 AN: 67998

Other (OTH) AF: 0.0938 AC: 198 AN: 2110

Alfa AF: 0.103 Hom.: 1289

Bravo AF: 0.0954

Asia WGS AF: 0.184 AC: 640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.26
DANN	Benign	0.21
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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: rs5995871; hg19: chr22-40922332; COSMIC: COSV107446965;