Variant 9-129069128-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001329990.2(MIGA2):c.1457T>C(p.Met486Thr) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

MIGA2
NM_001329990.2 missense, splice_region

Scores

Splicing: ADA: 0.9229

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.37

Variant links:

Genes affected

MIGA2 (HGNC:23621): (mitoguardin 2) Enables protein heterodimerization activity and protein homodimerization activity. Involved in mitochondrial fusion. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

MIGA2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIGA2	NM_001329990.2 linkuse as main transcript	c.1457T>C	p.Met486Thr	missense_variant, splice_region_variant	14/16	ENST00000684074.1	NP_001316919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIGA2	ENST00000684074.1 linkuse as main transcript	c.1457T>C	p.Met486Thr	missense_variant, splice_region_variant	14/16		NM_001329990.2	ENSP00000506871	P1	Q7L4E1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

251044

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135762

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:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727136

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:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Aug 10, 2021

The c.1457T>C (p.M486T) alteration is located in exon 14 (coding exon 13) of the MIGA2 gene. This alteration results from a T to C substitution at nucleotide position 1457, causing the methionine (M) at amino acid position 486 to be replaced by a threonine (T). 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

0.12

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.018

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.70

M_CAP

Benign

0.038

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.0

REVEL

Benign

0.20

Sift

Benign

0.095

Sift4G

Benign

0.13

Polyphen

0.39

Vest4

0.74

MutPred

0.54

Loss of stability (P = 0.06);

MVP

0.70

MPC

0.78

ClinPred

0.48

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.24

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.92

dbscSNV1_RF

Benign

0.72

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