Genetic Variant NM_019008.6:c.*2954T>G (chr22-39517277-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019008.6(MIEF1):c.*2954T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 197,370 control chromosomes in the GnomAD database, including 9,181 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 0.31 ( 7678 hom., cov: 33)

Exomes 𝑓: 0.24 ( 1503 hom. )

Consequence

MIEF1
NM_019008.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0730

Publications

16 publications found

Variant links:

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

MIEF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MIEF1	NM_019008.6 link	c.*2954T>G	3_prime_UTR_variant	Exon 6 of 6	ENST00000325301.7	NP_061881.2	Q9NQG6-1A0A024R1L3
MIEF1	NR_130789.2 link	n.4747T>G	non_coding_transcript_exon_variant	Exon 6 of 6
MIEF1	NR_130790.2 link	n.4897T>G	non_coding_transcript_exon_variant	Exon 7 of 7
MIEF1	NM_001304564.2 link	c.*1904T>G	3_prime_UTR_variant	Exon 7 of 7		NP_001291493.1	Q9NQG6B0QY95Q9H0J7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIEF1	ENST00000325301.7 link	c.*2954T>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_019008.6	ENSP00000327124.2		Q9NQG6-1

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47798

AN:

151994

Hom.:

7679

Cov.:

show subpopulations

Gnomad AFR

AF:

0.330

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.342

Gnomad EAS

AF:

0.178

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.316

GnomAD4 exome

AF:

0.237

AC:

10747

AN:

45258

Hom.:

1503

Cov.:

AF XY:

0.242

AC XY:

6040

AN XY:

24960

show subpopulations

African (AFR)

AF:

0.226

AC:

213

AN:

942

American (AMR)

AF:

0.198

AC:

441

AN:

2232

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

280

AN:

1010

East Asian (EAS)

AF:

0.130

AC:

205

AN:

1582

South Asian (SAS)

AF:

0.261

AC:

2384

AN:

9136

European-Finnish (FIN)

AF:

0.262

AC:

640

AN:

2440

Middle Eastern (MID)

AF:

0.220

AC:

AN:

168

European-Non Finnish (NFE)

AF:

0.236

AC:

6011

AN:

25428

Other (OTH)

AF:

0.231

AC:

536

AN:

2320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

381

763

1144

1526

1907

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.314

AC:

47820

AN:

152112

Hom.:

7678

Cov.:

AF XY:

0.314

AC XY:

23316

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.330

AC:

13692

AN:

41492

American (AMR)

AF:

0.292

AC:

4455

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

1184

AN:

3466

East Asian (EAS)

AF:

0.177

AC:

920

AN:

5190

South Asian (SAS)

AF:

0.335

AC:

1617

AN:

4822

European-Finnish (FIN)

AF:

0.331

AC:

3496

AN:

10554

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.314

AC:

21360

AN:

67988

Other (OTH)

AF:

0.315

AC:

665

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1697

3394

5091

6788

8485

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

494

988

1482

1976

2470

<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:

0.320

Hom.:

9749

Bravo

AF:

0.312

Asia WGS

AF:

0.322

AC:

1122

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.0

(source)

DANN

Benign

0.78

PhyloP100

0.073

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over