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GeneBe

7-91874103-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.016 ( 70 hom., cov: 32)
Exomes 𝑓: 0.0019 ( 97 hom. )

Consequence

MTERF1
NM_006980.5 missense

Scores

16

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.176
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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 id is 785222.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MTERF1NM_006980.5 linkuse as main transcriptc.691G>A p.Ala231Thr missense_variant 3/3 ENST00000351870.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MTERF1ENST00000351870.8 linkuse as main transcriptc.691G>A p.Ala231Thr missense_variant 3/31 NM_006980.5
MTERF1ENST00000419292.1 linkuse as main transcriptc.631G>A p.Ala211Thr missense_variant 2/21 P1
MTERF1ENST00000406735.6 linkuse as main transcriptc.631G>A p.Ala211Thr missense_variant 4/42 P1
MTERF1ENST00000454222.5 linkuse as main transcriptn.93+5952G>A intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0162
AC:
2459
AN:
152108
Hom.:
67
Cov.:
32
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
GnomAD3 exomes
AF:
0.00437
AC:
1097
AN:
250818
Hom.:
28
AF XY:
0.00348
AC XY:
473
AN XY:
135774
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 SAS exome
AF:
0.000294
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.:
97
Cov.:
34
AF XY:
0.00177
AC XY:
1284
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.0588
Gnomad4 AMR exome
AF:
0.00356
Gnomad4 ASJ exome
AF:
0.00180
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000278
Gnomad4 FIN exome
AF:
0.0000749
Gnomad4 NFE exome
AF:
0.000286
Gnomad4 OTH exome
AF:
0.00510
GnomAD4 genome
AF:
0.0163
AC:
2488
AN:
152226
Hom.:
70
Cov.:
32
AF XY:
0.0157
AC XY:
1171
AN XY:
74416
show subpopulations
Gnomad4 AFR
AF:
0.0560
Gnomad4 AMR
AF:
0.00576
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.000544
Gnomad4 OTH
AF:
0.0123
Alfa
AF:
0.00286
Hom.:
16
Bravo
AF:
0.0185
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.0486
AC:
214
ESP6500EA
AF:
0.000930
AC:
8
ExAC
AF:
0.00530
AC:
644
Asia WGS
AF:
0.00693
AC:
24
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000356

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.064
BayesDel_addAF
Benign
-0.77
T
BayesDel_noAF
Benign
-0.84
CADD
Benign
2.7
DANN
Benign
0.78
DEOGEN2
Benign
0.00034
T;T;T
Eigen
Benign
-2.0
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.014
N
MetaRNN
Benign
0.0021
T;T;T
MetaSVM
Benign
-0.96
T
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
0.95
N;N;N
REVEL
Benign
0.0090
Sift
Benign
0.42
T;T;T
Sift4G
Benign
0.64
T;T;T
Polyphen
0.0
.;B;.
Vest4
0.010
MVP
0.055
MPC
0.014
ClinPred
0.000016
T
GERP RS
-5.6
Varity_R
0.044
gMVP
0.25

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs17856025; hg19: chr7-91503417; COSMIC: COSV99065593; COSMIC: COSV99065593; API