rs5757949

Variant names:

• chr22-40424147-T-A
• rs5757949
• NM_020831.6:c.777+59A>T

Your query was ambiguous. Multiple possible variants found:

• chr22-40424147-T-A
• chr22-40424147-T-C
• chr22-40424147-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020831.6(MRTFA):​c.777+59A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MRTFA NM_020831.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.182
• Publications: 20 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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.777+59A>T		intron	N/A	NP_065882.2	A0A499FIJ6
	MRTFA	NM_001282661.3		c.777+59A>T		intron	N/A	NP_001269590.2	B0QY83
	MRTFA	NM_001318139.2		c.582+59A>T		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.777+59A>T		intron	N/A	ENSP00000347847.5	A0A499FIJ6
	MRTFA	ENST00000402042.7	TSL:1	c.777+59A>T		intron	N/A	ENSP00000385584.3	B0QY83
	MRTFA	ENST00000407029.7	TSL:1	c.477+59A>T		intron	N/A	ENSP00000385835.1	Q969V6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1336012 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 656644

African (AFR) AF: 0.00 AC: 0 AN: 28112

American (AMR) AF: 0.00 AC: 0 AN: 24948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20460

East Asian (EAS) AF: 0.00 AC: 0 AN: 34742

South Asian (SAS) AF: 0.00 AC: 0 AN: 66636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3810

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1053066

Other (OTH) AF: 0.00 AC: 0 AN: 55012

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.7
DANN	Benign	0.76
PhyloP100		0.18

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: rs5757949; hg19: chr22-40820151;