rs12157495

Variant names:

• chr22-40477572-T-C
• rs12157495
• NM_020831.6:c.242-14286A>G

Variant summary

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

The NM_001282662.3(MRTFA):​c.242-14286A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0377 in 152,152 control chromosomes in the GnomAD database, including 316 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 0.038 (316 hom., cov: 31)
• Consequence: MRTFA NM_001282662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.351
• Publications: 2 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: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRTFA	NM_020831.6	c.242-14286A>G		intron_variant	Intron 3 of 14	ENST00000355630.10	NP_065882.2
MRTFA	NM_001282661.3	c.242-14286A>G		intron_variant	Intron 3 of 13		NP_001269590.2
MRTFA	NM_001318139.2	c.47-14286A>G		intron_variant	Intron 1 of 12		NP_001305068.1
MRTFA	NM_001282662.3	c.242-14286A>G		intron_variant	Intron 3 of 14		NP_001269591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRTFA	ENST00000355630.10	c.242-14286A>G		intron_variant	Intron 3 of 14	1	NM_020831.6	ENSP00000347847.5

Frequencies

GnomAD3 genomes AF: 0.0375 AC: 5704 AN: 152034 Hom.: 309 Cov.: 31

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0227

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.00394

Gnomad OTH AF: 0.0378

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

GnomAD4 genome AF: 0.0377 AC: 5730 AN: 152152 Hom.: 316 Cov.: 31 AF XY: 0.0367 AC XY: 2730 AN XY: 74404

African (AFR) AF: 0.115 AC: 4769 AN: 41446

American (AMR) AF: 0.0227 AC: 347 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0648 AC: 225 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.00391 AC: 266 AN: 68008

Other (OTH) AF: 0.0369 AC: 78 AN: 2112

Alfa AF: 0.0293 Hom.: 29

Bravo AF: 0.0412

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.61
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: rs12157495; hg19: chr22-40873576;