dbSNP rs530570909: MTERF1:p.Gly222Arg (chr7-91874130-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006980.5(MTERF1):c.664G>C(p.Gly222Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G222S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

MTERF1
NM_006980.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.50

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.116229355).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTERF1	NM_006980.5 link	c.664G>C	p.Gly222Arg	missense_variant	Exon 3 of 3	ENST00000351870.8	NP_008911.1	Q99551

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTERF1	ENST00000351870.8 link	c.664G>C	p.Gly222Arg	missense_variant	Exon 3 of 3	1	NM_006980.5	ENSP00000248643.3		Q99551

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251188

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

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

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.5

DANN

Benign

0.91

DEOGEN2

Benign

0.091

T;T;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.75

.;T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.48

PROVEAN

Benign

0.37

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.21

T;T;T

Polyphen

0.86

.;P;.

Vest4

0.25

MutPred

0.63

.;Loss of catalytic residue at S224 (P = 0.0679);.;

MVP

0.18

MPC

0.064

ClinPred

0.17

GERP RS

-0.51

Varity_R

0.26

gMVP

0.59

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over