chr7-91874103-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006980.5(MTERF1):c.691G>A(p.Ala231Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00331 in 1,614,054 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A231V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.016 ( 70 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 97 hom. )

Consequence

MTERF1
NM_006980.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.176

Publications

7 publications found

Variant links:

Genes affected

MTERF1 (HGNC:21463): (mitochondrial transcription termination factor 1) This gene encodes a mitochondrial transcription termination factor. This protein participates in attenuating transcription from the mitochondrial genome; this attenuation allows higher levels of expression of 16S ribosomal RNA relative to the tRNA gene downstream. The product of this gene has three leucine zipper motifs bracketed by two basic domains that are all required for DNA binding. There is evidence that, for this protein, the zippers participate in intramolecular interactions that establish the three-dimensional structure required for DNA binding. [provided by RefSeq, Jul 2008]

MTERF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020922124).

BP6

Variant 7-91874103-C-T is Benign according to our data. Variant chr7-91874103-C-T is described in ClinVar as Benign. ClinVar VariationId is 785222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006980.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTERF1	NM_006980.5	MANE Select	c.691G>A	p.Ala231Thr	missense	Exon 3 of 3	NP_008911.1	Q99551
MTERF1	NM_001301134.2		c.631G>A	p.Ala211Thr	missense	Exon 2 of 2	NP_001288063.1	B4DPR9
MTERF1	NM_001301135.2		c.631G>A	p.Ala211Thr	missense	Exon 4 of 4	NP_001288064.1	B4DPR9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTERF1	ENST00000351870.8	TSL:1 MANE Select	c.691G>A	p.Ala231Thr	missense	Exon 3 of 3	ENSP00000248643.3	Q99551
MTERF1	ENST00000419292.1	TSL:1	c.631G>A	p.Ala211Thr	missense	Exon 2 of 2	ENSP00000414116.1	B4DPR9
MTERF1	ENST00000867199.1		c.691G>A	p.Ala231Thr	missense	Exon 3 of 3	ENSP00000537258.1

Frequencies

GnomAD3 genomes

AF:

0.0162

AC:

2459

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.0125

GnomAD2 exomes

AF:

0.00437

AC:

1097

AN:

250818

AF XY:

0.00348

show subpopulations

Gnomad AFR exome

AF:

0.0566

Gnomad AMR exome

AF:

0.00295

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000396

Gnomad OTH exome

AF:

0.00279

GnomAD4 exome

AF:

0.00195

AC:

2850

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

1284

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.0588

AC:

1969

AN:

33478

American (AMR)

AF:

0.00356

AC:

159

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00180

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.000278

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.0000749

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000286

AC:

318

AN:

1112000

Other (OTH)

AF:

0.00510

AC:

308

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

173

346

519

692

865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<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:

0.0163

AC:

2488

AN:

152226

Hom.:

Cov.:

AF XY:

0.0157

AC XY:

1171

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0560

AC:

2326

AN:

41518

American (AMR)

AF:

0.00576

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000544

AC:

AN:

68016

Other (OTH)

AF:

0.0123

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

110

221

331

442

552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00596

Hom.:

Bravo

AF:

0.0185

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0486

AC:

214

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.00530

AC:

644

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.7

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.00034

Eigen

Benign

-2.0

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.061

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.96

PhyloP100

0.18

PrimateAI

Benign

0.24

PROVEAN

Benign

0.95

REVEL

Benign

0.0090

Sift

Benign

0.42

Sift4G

Benign

0.64

Polyphen

0.0

Vest4

0.010

MVP

0.055

MPC

0.014

ClinPred

0.000016

GERP RS

-5.6

Varity_R

0.044

gMVP

0.25

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over