Variant 15-41696827-C-T 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.1817C>T(p.Ala606Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,599,752 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 9 hom. )

Consequence

MGA
ENST00000703841.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0130

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=0.0024363399).

BP6

Variant 15-41696827-C-T is Benign according to our data. Variant chr15-41696827-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 778487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGA	NM_001400225.1 linkuse as main transcript	c.1817C>T	p.Ala606Val	missense_variant	3/24	ENST00000703841.1	NP_001387154.1
MGA	XM_017022029.3 linkuse as main transcript	c.446C>T	p.Ala149Val	missense_variant	2/23		XP_016877518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGA	ENST00000703841.1 linkuse as main transcript	c.1817C>T	p.Ala606Val	missense_variant	3/24		NM_001400225.1	ENSP00000515495	A2

Frequencies

GnomAD3 genomes

AF:

0.00278

AC:

423

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00344

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00252

AC:

564

AN:

223542

Hom.:

AF XY:

0.00228

AC XY:

275

AN XY:

120536

show subpopulations

Gnomad AFR exome

AF:

0.000223

Gnomad AMR exome

AF:

0.00271

Gnomad ASJ exome

AF:

0.0111

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000836

Gnomad NFE exome

AF:

0.00336

Gnomad OTH exome

AF:

0.00320

GnomAD4 exome

AF:

0.00310

AC:

4482

AN:

1447510

Hom.:

Cov.:

AF XY:

0.00296

AC XY:

2126

AN XY:

718568

show subpopulations

Gnomad4 AFR exome

AF:

0.000451

Gnomad4 AMR exome

AF:

0.00270

Gnomad4 ASJ exome

AF:

0.0104

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000238

Gnomad4 FIN exome

AF:

0.000626

Gnomad4 NFE exome

AF:

0.00350

Gnomad4 OTH exome

AF:

0.00295

GnomAD4 genome

AF:

0.00278

AC:

423

AN:

152242

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

205

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.000795

Gnomad4 AMR

AF:

0.00634

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00344

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00353

Hom.:

Bravo

AF:

0.00308

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000266

AC:

ESP6500EA

AF:

0.00364

AC:

ExAC

AF:

0.00225

AC:

271

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2023	MGA: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.3

DANN

Benign

0.94

DEOGEN2

Benign

0.067

.;T;.;.;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.75

T;T;T;T;.;.

M_CAP

Benign

0.0051

MetaRNN

Benign

0.0024

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

.;.;L;L;L;L

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.8

N;N;N;N;N;N

REVEL

Benign

0.053

Sift

Benign

0.39

T;T;T;T;T;T

Sift4G

Benign

0.94

T;T;T;T;T;T

Vest4

0.12, 0.13, 0.12

MVP

0.093

MPC

0.094

ClinPred

0.0054

GERP RS

-0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.14

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