rs6001946

Variant names:

• chr22-40507417-A-G
• rs6001946
• NM_020831.6:c.242-44131T>C

Your query was ambiguous. Multiple possible variants found:

• chr22-40507417-A-G
• chr22-40507417-A-T

Variant summary

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

The NM_020831.6(MRTFA):​c.242-44131T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 151,918 control chromosomes in the GnomAD database, including 1,261 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 0.12 (1261 hom., cov: 30)
• Consequence: MRTFA NM_020831.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• 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 Gene-Disease associations (from GenCC):

• immunodeficiency 66

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRTFA	NM_020831.6	MANE Select	c.242-44131T>C		intron	N/A	NP_065882.2	A0A499FIJ6
	MRTFA	NM_001282661.3		c.242-44131T>C		intron	N/A	NP_001269590.2	B0QY83
	MRTFA	NM_001318139.2		c.46+26173T>C		intron	N/A	NP_001305068.1	W0Z7M9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRTFA	ENST00000355630.10	TSL:1 MANE Select	c.242-44131T>C		intron	N/A	ENSP00000347847.5	A0A499FIJ6
	MRTFA	ENST00000402042.7	TSL:1	c.242-44131T>C		intron	N/A	ENSP00000385584.3	B0QY83
	MRTFA	ENST00000463769.7	TSL:1	c.242-44131T>C		intron	N/A	ENSP00000498788.2	A0A494C0Z8

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18252 AN: 151800 Hom.: 1253 Cov.: 30

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.120 AC: 18287 AN: 151918 Hom.: 1261 Cov.: 30 AF XY: 0.126 AC XY: 9319 AN XY: 74244

African (AFR) AF: 0.133 AC: 5503 AN: 41426

American (AMR) AF: 0.109 AC: 1664 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 451 AN: 3468

East Asian (EAS) AF: 0.244 AC: 1258 AN: 5166

South Asian (SAS) AF: 0.123 AC: 595 AN: 4820

European-Finnish (FIN) AF: 0.154 AC: 1619 AN: 10532

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6800 AN: 67936

Other (OTH) AF: 0.105 AC: 221 AN: 2110

Alfa AF: 0.0968 Hom.: 375

Bravo AF: 0.114

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.49
PhyloP100		-0.50
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: rs6001946; hg19: chr22-40903421;