Variant 15-41669882-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000703841.1(MGA):c.988C>G(p.Arg330Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00716 in 1,613,900 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0074 ( 63 hom. )

Consequence

MGA
ENST00000703841.1 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.661

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0068923235).

BP6

Variant 15-41669882-C-G is Benign according to our data. Variant chr15-41669882-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 789331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGA	NM_001400225.1 linkuse as main transcript	c.988C>G	p.Arg330Gly	missense_variant	2/24	ENST00000703841.1	NP_001387154.1
MGA	XM_017022029.3 linkuse as main transcript	c.-307-26193C>G		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.988C>G	p.Arg330Gly	missense_variant	2/24		NM_001400225.1	ENSP00000515495	A2

Frequencies

GnomAD3 genomes

AF:

0.00464

AC:

706

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.000755

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00837

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00403

AC:

998

AN:

247396

Hom.:

AF XY:

0.00395

AC XY:

531

AN XY:

134426

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00121

Gnomad FIN exome

AF:

0.000835

Gnomad NFE exome

AF:

0.00717

Gnomad OTH exome

AF:

0.00497

GnomAD4 exome

AF:

0.00743

AC:

10857

AN:

1461660

Hom.:

Cov.:

AF XY:

0.00714

AC XY:

5189

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.00116

Gnomad4 AMR exome

AF:

0.00284

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00137

Gnomad4 FIN exome

AF:

0.00133

Gnomad4 NFE exome

AF:

0.00910

Gnomad4 OTH exome

AF:

0.00628

GnomAD4 genome

AF:

0.00464

AC:

706

AN:

152240

Hom.:

Cov.:

AF XY:

0.00394

AC XY:

293

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.000755

Gnomad4 NFE

AF:

0.00837

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00704

Hom.:

Bravo

AF:

0.00471

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.00934

AC:

ESP6500AA

AF:

0.00215

AC:

ESP6500EA

AF:

0.00770

AC:

ExAC

AF:

0.00387

AC:

467

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00676

EpiControl

AF:

0.00694

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 04, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.18

.;T;.;.;.;.

Eigen

Benign

-0.063

Eigen_PC

Benign

0.044

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.79

T;T;T;T;.;.

M_CAP

Benign

0.060

MetaRNN

Benign

0.0069

T;T;T;T;T;T

MetaSVM

Benign

-0.43

MutationAssessor

Benign

0.55

.;.;N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-2.8

D;D;N;N;N;N

REVEL

Uncertain

0.41

Sift

Uncertain

0.0030

D;D;D;D;D;D

Sift4G

Uncertain

0.046

D;T;D;D;D;D

Vest4

0.27, 0.23, 0.28, 0.24

MVP

0.23

MPC

0.12

ClinPred

0.035

GERP RS

4.7

gMVP

0.22

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