22-40480230-T-C

Variant names:

• chr22-40480230-T-C
• rs6001930
• NM_020831.6:c.242-16944A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020831.6(MRTFA):​c.242-16944A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 151,988 control chromosomes in the GnomAD database, including 1,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1294 hom., cov: 31)
• Consequence: MRTFA NM_020831.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.353
• Publications: 91 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 22-40480230-T-C is Benign according to our data. Variant chr22-40480230-T-C is described in ClinVar as Benign. ClinVar VariationId is 225836.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 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.242-16944A>G		intron	N/A	NP_065882.2	A0A499FIJ6
	MRTFA	NM_001282661.3		c.242-16944A>G		intron	N/A	NP_001269590.2	B0QY83
	MRTFA	NM_001318139.2		c.47-16944A>G		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.242-16944A>G		intron	N/A	ENSP00000347847.5	A0A499FIJ6
	MRTFA	ENST00000402042.7	TSL:1	c.242-16944A>G		intron	N/A	ENSP00000385584.3	B0QY83
	MRTFA	ENST00000463769.7	TSL:1	c.242-16944A>G		intron	N/A	ENSP00000498788.2	A0A494C0Z8

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18428 AN: 151874 Hom.: 1287 Cov.: 31

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.183

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.121 AC: 18458 AN: 151988 Hom.: 1294 Cov.: 31 AF XY: 0.127 AC XY: 9402 AN XY: 74286

African (AFR) AF: 0.135 AC: 5581 AN: 41402

American (AMR) AF: 0.110 AC: 1677 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 445 AN: 3466

East Asian (EAS) AF: 0.245 AC: 1269 AN: 5178

South Asian (SAS) AF: 0.124 AC: 594 AN: 4806

European-Finnish (FIN) AF: 0.155 AC: 1630 AN: 10544

Middle Eastern (MID) AF: 0.166 AC: 48 AN: 290

European-Non Finnish (NFE) AF: 0.101 AC: 6867 AN: 68002

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

Alfa AF: 0.108 Hom.: 2663

Bravo AF: 0.115

Asia WGS AF: 0.187 AC: 649 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.71
PhyloP100		-0.35
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: rs6001930; hg19: chr22-40876234;