Genetic Variant MRTFA:p.His1026Asp (chr22-40411410-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020831.6(MRTFA):c.3076C>G(p.His1026Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,413,876 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H1026Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

MRTFA
NM_020831.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.94

Publications

0 publications found

Variant links:

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)

MRTFA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRTFA	NM_020831.6 link	c.3076C>G	p.His1026Asp	missense_variant	Exon 15 of 15	ENST00000355630.10	NP_065882.2	Q969V6A4FUJ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRTFA	ENST00000355630.10 link	c.3076C>G	p.His1026Asp	missense_variant	Exon 15 of 15	1	NM_020831.6	ENSP00000347847.5		A0A499FIJ6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.07e-7

AC:

AN:

1413876

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

695206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32714

American (AMR)

AF:

0.00

AC:

AN:

42262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23520

East Asian (EAS)

AF:

0.00

AC:

AN:

38838

South Asian (SAS)

AF:

0.00

AC:

AN:

80640

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52108

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5564

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1080058

Other (OTH)

AF:

0.0000172

AC:

AN:

58172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.57

D;T;T;D;T;T

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

.;D;D;D;D;D

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.64

D;D;D;D;D;D

MetaSVM

Benign

-0.73

PhyloP100

8.9

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-6.1

D;.;D;D;.;.

REVEL

Uncertain

0.32

Sift

Benign

0.33

T;.;T;T;.;.

Sift4G

Benign

0.21

T;T;T;T;D;T

Polyphen

0.99

D;.;D;D;.;.

Vest4

0.79

MutPred

0.43

Gain of disorder (P = 0.0446);.;.;Gain of disorder (P = 0.0446);.;.;

MVP

0.52

MPC

0.34

ClinPred

0.97

GERP RS

4.8

Varity_R

0.68

Mutation Taster

=65/35

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over