Genetic Variant NM_001416120.1:c.545T>C (chr1-77813737-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001416120.1(MIGA1):c.545T>C(p.Met182Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,186 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

MIGA1
NM_001416120.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.89

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001416120.1. 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.545T>C	p.Met182Thr	missense	Exon 6 of 16	NP_001403049.1	A0A2R8YF99
MIGA1	NM_001270384.2		c.641T>C	p.Met214Thr	missense	Exon 6 of 16	NP_001257313.1
MIGA1	NM_198549.4		c.641T>C	p.Met214Thr	missense	Exon 6 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.545T>C	p.Met182Thr	missense	Exon 6 of 16	ENSP00000359827.4	A0A2R8YF99
MIGA1	ENST00000443751.4	TSL:1	c.545T>C	p.Met182Thr	missense	Exon 6 of 16	ENSP00000393675.4	F8W7S1
MIGA1	ENST00000710932.1		c.641T>C	p.Met214Thr	missense	Exon 6 of 16	ENSP00000518551.1	Q8NAN2-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

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

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.71

MetaSVM

Benign

-0.84

PhyloP100

6.9

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-4.6

REVEL

Uncertain

0.38

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

0.96

Vest4

0.91

MVP

0.76

MPC

0.45

ClinPred

0.99

GERP RS

5.0

Varity_R

0.75

gMVP

0.80

Mutation Taster

=35/65

disease causing

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over