1-77874855-C-A

Variant names:

• chr1-77874855-C-A
• rs151188678
• NM_001416120.1:c.1594C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001416120.1(MIGA1):​c.1594C>A​(p.Leu532Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000881 in 1,612,340 control chromosomes in the GnomAD database, including 2 homozygotes. 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 0.00037 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00093 (1 hom.)
• Consequence: MIGA1 NM_001416120.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.045650214).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIGA1	NM_001416120.1	MANE Select	c.1594C>A	p.Leu532Ile	missense	Exon 16 of 16	NP_001403049.1	A0A2R8YF99
	MIGA1	NM_001270384.2		c.1693C>A	p.Leu565Ile	missense	Exon 16 of 16	NP_001257313.1
	MIGA1	NM_198549.4		c.1690C>A	p.Leu564Ile	missense	Exon 16 of 16	NP_940951.1	Q8NAN2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIGA1	ENST00000370791.9	TSL:1 MANE Select	c.1594C>A	p.Leu532Ile	missense	Exon 16 of 16	ENSP00000359827.4	A0A2R8YF99
	MIGA1	ENST00000443751.4	TSL:1	c.1597C>A	p.Leu533Ile	missense	Exon 16 of 16	ENSP00000393675.4	F8W7S1
	MIGA1	ENST00000710932.1		c.1690C>A	p.Leu564Ile	missense	Exon 16 of 16	ENSP00000518551.1	Q8NAN2-1

Frequencies

GnomAD3 genomes AF: 0.000375 AC: 57 AN: 152050 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000145

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: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000677

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000445 AC: 111 AN: 249336 AF XY: 0.000489

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.000350

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000278

Gnomad NFE exome AF: 0.000745

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000933 AC: 1363 AN: 1460290 Hom.: 1 Cov.: 31 AF XY: 0.000885 AC XY: 643 AN XY: 726330

African (AFR) AF: 0.000150 AC: 5 AN: 33418

American (AMR) AF: 0.000337 AC: 15 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 85878

European-Finnish (FIN) AF: 0.000393 AC: 21 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00115 AC: 1273 AN: 1111152

Other (OTH) AF: 0.000812 AC: 49 AN: 60344

GnomAD4 genome AF: 0.000375 AC: 57 AN: 152050 Hom.: 1 Cov.: 32 AF XY: 0.000337 AC XY: 25 AN XY: 74264

African (AFR) AF: 0.000145 AC: 6 AN: 41394

American (AMR) AF: 0.000197 AC: 3 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000677 AC: 46 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000623 Hom.: 0

Bravo AF: 0.000416

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.000371 AC: 45

EpiCase AF: 0.00136

EpiControl AF: 0.000416

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.4
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.013
Sift	Benign	0.49	T
Sift4G	Benign	0.21	T
Polyphen		0.013	B
Vest4		0.26
MVP		0.27
MPC		0.16
ClinPred		0.012	T
GERP RS		2.6
Varity_R		0.10
gMVP		0.19
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs151188678; hg19: chr1-78340540;