Variant 1-77801478-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000370791.9(MIGA1):c.247G>C(p.Glu83Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00143 in 1,602,742 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00091 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 5 hom. )

Consequence

MIGA1
ENST00000370791.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.91

Variant links:

Genes affected

MIGA1 (HGNC:24741): (mitoguardin 1) Enables protein heterodimerization activity and protein homodimerization activity. Involved in mitochondrial fusion. Located in mitochondrion. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

MIGA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.035810947).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIGA1	NM_001416120.1 linkuse as main transcript	c.247G>C	p.Glu83Gln	missense_variant	3/16	ENST00000370791.9	NP_001403049.1
MIGA1	NM_001270384.2 linkuse as main transcript	c.343G>C	p.Glu115Gln	missense_variant	3/16		NP_001257313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIGA1	ENST00000370791.9 linkuse as main transcript	c.247G>C	p.Glu83Gln	missense_variant	3/16	1	NM_001416120.1	ENSP00000359827	P4	Q8NAN2-1

Frequencies

GnomAD3 genomes

AF:

0.000914

AC:

139

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00162

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000598

AC:

143

AN:

239060

Hom.:

AF XY:

0.000633

AC XY:

AN XY:

129622

show subpopulations

Gnomad AFR exome

AF:

0.0000631

Gnomad AMR exome

AF:

0.000394

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000525

Gnomad NFE exome

AF:

0.00103

Gnomad OTH exome

AF:

0.000856

GnomAD4 exome

AF:

0.00148

AC:

2146

AN:

1450584

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

1035

AN XY:

721598

show subpopulations

Gnomad4 AFR exome

AF:

0.000366

Gnomad4 AMR exome

AF:

0.000417

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000814

Gnomad4 NFE exome

AF:

0.00177

Gnomad4 OTH exome

AF:

0.00189

GnomAD4 genome

AF:

0.000914

AC:

139

AN:

152158

Hom.:

Cov.:

AF XY:

0.000726

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.000434

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00162

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.00132

Hom.:

Bravo

AF:

0.000876

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000552

AC:

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

Jun 11, 2021

The c.343G>C (p.E115Q) alteration is located in exon 3 (coding exon 3) of the MIGA1 gene. This alteration results from a G to C substitution at nucleotide position 343, causing the glutamic acid (E) at amino acid position 115 to be replaced by a glutamine (Q). 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

0.10

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

T;T;.;.;.;.;.

Eigen

Benign

0.098

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.76

.;T;T;T;T;T;T

M_CAP

Benign

0.0047

MetaRNN

Benign

0.036

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.50

N;.;.;.;.;.;.

REVEL

Benign

0.029

Sift

Benign

0.17

T;.;.;.;.;.;.

Sift4G

Benign

0.25

T;T;.;.;.;.;.

Polyphen

0.32

B;.;.;.;.;.;.

Vest4

0.48

MVP

0.42

MPC

0.16

ClinPred

0.014

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.078

gMVP

0.29

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

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