dbSNP rs2232090: MIEF1:p.Val262Val (chr22-39513717-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_019008.6(MIEF1):c.786C>T(p.Val262Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00513 in 1,614,116 control chromosomes in the GnomAD database, including 358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 183 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 175 hom. )

Consequence

MIEF1
NM_019008.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.345

Publications

1 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 22-39513717-C-T is Benign according to our data. Variant chr22-39513717-C-T is described in ClinVar as Benign. ClinVar VariationId is 783888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.345 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIEF1	NM_019008.6 link	c.786C>T	p.Val262Val	synonymous_variant	Exon 6 of 6	ENST00000325301.7	NP_061881.2	Q9NQG6-1A0A024R1L3
MIEF1	NM_001304564.2 link	c.786C>T	p.Val262Val	synonymous_variant	Exon 6 of 7		NP_001291493.1	Q9NQG6B0QY95Q9H0J7
MIEF1	NR_130789.2 link	n.1187C>T		non_coding_transcript_exon_variant	Exon 6 of 6
MIEF1	NR_130790.2 link	n.1337C>T		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIEF1	ENST00000325301.7 link	c.786C>T	p.Val262Val	synonymous_variant	Exon 6 of 6	1	NM_019008.6	ENSP00000327124.2		Q9NQG6-1

Frequencies

GnomAD3 genomes

AF:

0.0261

AC:

3974

AN:

152156

Hom.:

182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0907

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00968

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.0182

GnomAD2 exomes

AF:

0.00707

AC:

1776

AN:

251234

AF XY:

0.00503

show subpopulations

Gnomad AFR exome

AF:

0.0957

Gnomad AMR exome

AF:

0.00434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00294

AC:

4298

AN:

1461842

Hom.:

175

Cov.:

AF XY:

0.00259

AC XY:

1882

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.0948

AC:

3173

AN:

33474

American (AMR)

AF:

0.00496

AC:

222

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.000568

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00641

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000372

AC:

414

AN:

1111990

Other (OTH)

AF:

0.00664

AC:

401

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

285

569

854

1138

1423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

208

312

416

520

<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:

0.0261

AC:

3979

AN:

152274

Hom.:

183

Cov.:

AF XY:

0.0255

AC XY:

1901

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0906

AC:

3763

AN:

41536

American (AMR)

AF:

0.00967

AC:

148

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000382

AC:

AN:

68028

Other (OTH)

AF:

0.0180

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

187

375

562

750

937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0143

Hom.:

Bravo

AF:

0.0295

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

8.5

(source)

DANN

Benign

0.75

PhyloP100

0.34

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over