Variant 7-91873629-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_006980.5(MTERF1):c.1165G>A(p.Glu389Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,455,816 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

MTERF1
NM_006980.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.156

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:

MTERF1 (HGNC:):

MTERF1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030868083).

BP6

Variant 7-91873629-C-T is Benign according to our data. Variant chr7-91873629-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3296573.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTERF1	NM_006980.5 linkuse as main transcript	c.1165G>A	p.Glu389Lys	missense_variant	3/3	ENST00000351870.8	NP_008911.1	Q99551

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MTERF1	ENST00000351870.8 linkuse as main transcript	c.1165G>A	p.Glu389Lys	missense_variant	3/3	1	NM_006980.5	ENSP00000248643.3	Q99551
MTERF1	ENST00000419292.1 linkuse as main transcript	c.1105G>A	p.Glu369Lys	missense_variant	2/2	1		ENSP00000414116.1	B4DPR9
MTERF1	ENST00000406735.6 linkuse as main transcript	c.1105G>A	p.Glu369Lys	missense_variant	4/4	2		ENSP00000384986.2	B4DPR9
MTERF1	ENST00000454222.5 linkuse as main transcript	n.93+6426G>A		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

243520

Hom.:

AF XY:

0.00000760

AC XY:

AN XY:

131524

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000221

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1455816

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723614

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 16, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.70

CADD

Benign

1.9

DANN

Benign

0.76

DEOGEN2

Benign

0.016

T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.63

.;T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.031

T;T;T

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.047

Sift

Benign

0.13

T;T;T

Sift4G

Benign

0.82

T;T;T

Polyphen

0.0010

.;B;.

Vest4

0.092

MutPred

0.52

.;Gain of disorder (P = 0.0808);.;

MVP

0.099

MPC

0.015

ClinPred

0.011

GERP RS

-4.4

Varity_R

0.069

gMVP

0.28

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over