Genetic Variant MIGA1:c.-65G>C (chr1-77779687-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001270384.2(MIGA1):c.32G>C(p.Ser11Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000126 in 1,589,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

MIGA1
NM_001270384.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

Publications

0 publications found

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:

RNA5SP21 (HGNC:42589): (RNA, 5S ribosomal pseudogene 21)

RNA5SP21 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07430866).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270384.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIGA1	NM_001416120.1	MANE Select	c.-65G>C		5_prime_UTR	Exon 1 of 16	NP_001403049.1	A0A2R8YF99
MIGA1	NM_001270384.2		c.32G>C	p.Ser11Thr	missense	Exon 1 of 16	NP_001257313.1
MIGA1	NM_198549.4		c.32G>C	p.Ser11Thr	missense	Exon 1 of 16	NP_940951.1	Q8NAN2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIGA1	ENST00000370791.9	TSL:1 MANE Select	c.-65G>C		5_prime_UTR	Exon 1 of 16	ENSP00000359827.4	A0A2R8YF99
MIGA1	ENST00000443751.4	TSL:1	c.-65G>C		5_prime_UTR	Exon 1 of 16	ENSP00000393675.4	F8W7S1
MIGA1	ENST00000710932.1		c.32G>C	p.Ser11Thr	missense	Exon 1 of 16	ENSP00000518551.1	Q8NAN2-1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000439

AC:

AN:

205134

AF XY:

0.0000628

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000889

Gnomad OTH exome

AF:

0.000192

GnomAD4 exome

AF:

0.000126

AC:

181

AN:

1437610

Hom.:

Cov.:

AF XY:

0.000133

AC XY:

AN XY:

712514

show subpopulations

African (AFR)

AF:

0.0000605

AC:

AN:

33078

American (AMR)

AF:

0.0000242

AC:

AN:

41310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25620

East Asian (EAS)

AF:

0.00

AC:

AN:

38612

South Asian (SAS)

AF:

0.00

AC:

AN:

82318

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.000156

AC:

172

AN:

1100272

Other (OTH)

AF:

0.000101

AC:

AN:

59502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000125

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68016

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000670

Hom.:

Bravo

AF:

0.0000869

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000229

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000249

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.019

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.40

M_CAP

Benign

0.031

MetaRNN

Benign

0.074

MetaSVM

Benign

-0.98

PhyloP100

4.0

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.030

REVEL

Benign

0.11

Sift

Benign

0.21

Sift4G

Benign

0.92

Polyphen

0.0030

Vest4

0.14

MVP

0.24

MPC

0.082

ClinPred

0.084

GERP RS

3.0

PromoterAI

-0.37

Neutral

(source)

Varity_R

0.075

gMVP

0.17

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over