22-39517415-C-T

Variant names:

• chr22-39517415-C-T
• rs710192
• NM_019008.6:c.*3092C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019008.6(MIEF1):​c.*3092C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 315,248 control chromosomes in the GnomAD database, including 13,389 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (6853 hom., cov: 32)
  • Exomes 𝑓: 0.27 (6536 hom.)
• Consequence: MIEF1 NM_019008.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 14 publications found

Genes affected

MIEF1 (HGNC:25979): (mitochondrial elongation factor 1) Enables ADP binding activity; GDP binding activity; and identical protein binding activity. Involved in several processes, including positive regulation of mitochondrial fission; positive regulation of mitochondrial translation; and positive regulation of protein targeting to membrane. Located in mitochondrial matrix and mitochondrial outer membrane. Colocalizes with mitochondrial large ribosomal subunit. [provided by Alliance of Genome Resources, Apr 2022]

MIEF1 Gene-Disease associations (from GenCC):

• optic atrophy 14

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019008.6. 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
	MIEF1	NM_019008.6	MANE Select	c.*3092C>T		3_prime_UTR	Exon 6 of 6	NP_061881.2
	MIEF1	NM_001304564.2		c.*2042C>T		3_prime_UTR	Exon 7 of 7	NP_001291493.1	B0QY95
	MIEF1	NR_130789.2		n.4885C>T		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIEF1	ENST00000325301.7	TSL:1 MANE Select	c.*3092C>T		3_prime_UTR	Exon 6 of 6	ENSP00000327124.2	Q9NQG6-1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45198 AN: 151930 Hom.: 6858 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.304

GnomAD4 exome AF: 0.273 AC: 44617 AN: 163200 Hom.: 6536 Cov.: 0 AF XY: 0.279 AC XY: 25481 AN XY: 91434

African (AFR) AF: 0.205 AC: 698 AN: 3398

American (AMR) AF: 0.227 AC: 1784 AN: 7850

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 1082 AN: 3848

East Asian (EAS) AF: 0.140 AC: 692 AN: 4946

South Asian (SAS) AF: 0.296 AC: 10151 AN: 34278

European-Finnish (FIN) AF: 0.306 AC: 6207 AN: 20294

Middle Eastern (MID) AF: 0.289 AC: 187 AN: 648

European-Non Finnish (NFE) AF: 0.272 AC: 21927 AN: 80716

Other (OTH) AF: 0.262 AC: 1889 AN: 7222

GnomAD4 genome AF: 0.297 AC: 45205 AN: 152048 Hom.: 6853 Cov.: 32 AF XY: 0.296 AC XY: 22026 AN XY: 74298

African (AFR) AF: 0.274 AC: 11366 AN: 41456

American (AMR) AF: 0.281 AC: 4301 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1188 AN: 3472

East Asian (EAS) AF: 0.176 AC: 915 AN: 5186

South Asian (SAS) AF: 0.330 AC: 1593 AN: 4822

European-Finnish (FIN) AF: 0.332 AC: 3500 AN: 10544

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21291 AN: 67970

Other (OTH) AF: 0.302 AC: 637 AN: 2110

Alfa AF: 0.310 Hom.: 28349

Bravo AF: 0.292

Asia WGS AF: 0.314 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.65
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs710192; hg19: chr22-39913420;