22-40622161-T-C

Variant names:

• chr22-40622161-T-C
• rs133040
• NM_020831.6:c.-84+14317A>G

Variant summary

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

The NM_020831.6(MRTFA):​c.-84+14317A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,034 control chromosomes in the GnomAD database, including 7,451 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 0.29 (7451 hom., cov: 31)
• Consequence: MRTFA NM_020831.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.671
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 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.-84+14317A>G		intron	N/A	NP_065882.2	A0A499FIJ6
	MRTFA	NM_001282661.3		c.-84+14317A>G		intron	N/A	NP_001269590.2	B0QY83
	MRTFA	NM_001282662.3		c.-84+14317A>G		intron	N/A	NP_001269591.2	A0A494BZX7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRTFA	ENST00000355630.10	TSL:1 MANE Select	c.-84+14317A>G		intron	N/A	ENSP00000347847.5	A0A499FIJ6
	MRTFA	ENST00000402042.7	TSL:1	c.-84+14317A>G		intron	N/A	ENSP00000385584.3	B0QY83
	MRTFA	ENST00000463769.7	TSL:1	c.-22+14317A>G		intron	N/A	ENSP00000498788.2	A0A494C0Z8

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43697 AN: 151916 Hom.: 7458 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.287 AC: 43684 AN: 152034 Hom.: 7451 Cov.: 31 AF XY: 0.287 AC XY: 21313 AN XY: 74306

African (AFR) AF: 0.128 AC: 5324 AN: 41520

American (AMR) AF: 0.269 AC: 4109 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1338 AN: 3468

East Asian (EAS) AF: 0.626 AC: 3223 AN: 5150

South Asian (SAS) AF: 0.236 AC: 1140 AN: 4824

European-Finnish (FIN) AF: 0.337 AC: 3557 AN: 10560

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23923 AN: 67948

Other (OTH) AF: 0.322 AC: 680 AN: 2114

Alfa AF: 0.312 Hom.: 2941

Bravo AF: 0.279

Asia WGS AF: 0.342 AC: 1187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.40
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs133040;

hg19: chr22-41018165;