1-77813737-T-C

Position:

• chr1-77813737-T-C

Variant summary

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

The NM_198549.4(MIGA1):​c.641T>C​(p.Met214Thr) 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_198549.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.89

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 (HGNC:):

ACMG classification

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
MIGA1	NM_198549.4	c.641T>C	p.Met214Thr	missense_variant	6/16	ENST00000370791.8	NP_940951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIGA1	ENST00000370791.9	c.545T>C	p.Met182Thr	missense_variant	6/16	1		ENSP00000359827.4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152186 Hom.: 0 Cov.: 32

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.: 31

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74328

Gnomad4 AFR AF: 0.0000482

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.641T>C (p.M214T) alteration is located in exon 6 (coding exon 6) of the MIGA1 gene. This alteration results from a T to C substitution at nucleotide position 641, causing the methionine (M) at amino acid position 214 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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T;T;.;.;.;.;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	.;D;D;D;D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.71	D;D;D;D;D;D;D
MetaSVM	Benign	-0.84	T
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-4.6	D;.;.;.;.;.;.
REVEL	Uncertain	0.38
Sift	Uncertain	0.0010	D;.;.;.;.;.;.
Sift4G	Uncertain	0.0030	D;D;.;.;.;.;.
Polyphen		0.96	D;.;.;.;.;.;.
Vest4		0.91
MVP		0.76
MPC		0.45
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.75
gMVP		0.80

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

Other links and lift over

dbSNP: rs138084686; hg19: chr1-78279422; COSMIC: COSV105284427; COSMIC: COSV105284427;