rs6001930

Positions:

• chr22-40480230-T-C
• chr22-40480230-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRTFA	NM_020831.6	c.242-16944A>G		intron_variant		ENST00000355630.10	NP_065882.2
MRTFA	NM_001282661.3	c.242-16944A>G		intron_variant			NP_001269590.2
MRTFA	NM_001282662.3	c.242-16944A>G		intron_variant			NP_001269591.2
MRTFA	NM_001318139.2	c.47-16944A>G		intron_variant			NP_001305068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRTFA	ENST00000355630.10	c.242-16944A>G		intron_variant		1	NM_020831.6	ENSP00000347847

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

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.105

Alfa AF: 0.104 Hom.: 960

Bravo AF: 0.115

Asia WGS AF: 0.187 AC: 649 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs6001930; hg19: chr22-40876234;