Genetic Variant NM_006980.5:c.800G>A (chr7-91873994-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_006980.5(MTERF1):c.800G>A(p.Ser267Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 6.8e-7 ( 0 hom. )

Consequence

MTERF1
NM_006980.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0640

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027370214).

BP6

Variant 7-91873994-C-T is Benign according to our data. Variant chr7-91873994-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3875329.Status of the report is criteria_provided_single_submitter, 1 stars.

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.800G>A	p.Ser267Asn	missense	Exon 3 of 3	NP_008911.1	Q99551
MTERF1	NM_001301134.2		c.740G>A	p.Ser247Asn	missense	Exon 2 of 2	NP_001288063.1	B4DPR9
MTERF1	NM_001301135.2		c.740G>A	p.Ser247Asn	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.800G>A	p.Ser267Asn	missense	Exon 3 of 3	ENSP00000248643.3	Q99551
MTERF1	ENST00000419292.1	TSL:1	c.740G>A	p.Ser247Asn	missense	Exon 2 of 2	ENSP00000414116.1	B4DPR9
MTERF1	ENST00000867199.1		c.800G>A	p.Ser267Asn	missense	Exon 3 of 3	ENSP00000537258.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461770

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727176

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111996

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.0000468

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.051

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.0010

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.53

M_CAP

Benign

0.0023

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.92

PhyloP100

0.064

PrimateAI

Benign

0.27

PROVEAN

Benign

1.0

REVEL

Benign

0.061

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.035

MutPred

0.38

Gain of catalytic residue at S267 (P = 0.0393)

MVP

0.19

MPC

0.014

ClinPred

0.022

GERP RS

-0.99

Varity_R

0.032

gMVP

0.19

Mutation Taster

=94/6

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over