Variant 15-41669733-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000703841.1(MGA):c.839A>C(p.Glu280Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,461,426 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 1 hom. )

Consequence

MGA
ENST00000703841.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.21

Variant links:

Genes affected

MGA (HGNC:14010): (MAX dimerization protein MGA) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in cell fate specification and positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Part of MLL1 complex. [provided by Alliance of Genome Resources, Apr 2022]

MGA links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2151337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGA	NM_001400225.1 linkuse as main transcript	c.839A>C	p.Glu280Ala	missense_variant	2/24	ENST00000703841.1	NP_001387154.1
MGA	XM_017022029.3 linkuse as main transcript	c.-307-26342A>C		intron_variant			XP_016877518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGA	ENST00000703841.1 linkuse as main transcript	c.839A>C	p.Glu280Ala	missense_variant	2/24		NM_001400225.1	ENSP00000515495	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000282

AC:

AN:

248386

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134780

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461426

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726984

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000244

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000414

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.839A>C (p.E280A) alteration is located in exon 2 (coding exon 1) of the MGA gene. This alteration results from a A to C substitution at nucleotide position 839, causing the glutamic acid (E) at amino acid position 280 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

.;T;.;.;.;.

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.90

D;D;D;D;.;.

M_CAP

Benign

0.052

MetaRNN

Benign

0.22

T;T;T;T;T;T

MetaSVM

Uncertain

0.33

MutationAssessor

Benign

2.0

.;.;M;M;M;M

MutationTaster

Benign

0.98

D;D;D;D;D

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.1

D;D;D;D;D;D

REVEL

Uncertain

0.41

Sift

Uncertain

0.0070

D;D;D;D;D;D

Sift4G

Uncertain

0.051

T;T;D;D;D;D

Vest4

0.35, 0.27, 0.32, 0.29

MutPred

0.18

Gain of MoRF binding (P = 0.0446);Gain of MoRF binding (P = 0.0446);Gain of MoRF binding (P = 0.0446);Gain of MoRF binding (P = 0.0446);Gain of MoRF binding (P = 0.0446);Gain of MoRF binding (P = 0.0446);

MVP

0.34

MPC

0.13

ClinPred

0.33

GERP RS

5.7

gMVP

0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over