7-91874103-C-T

Position:

• chr7-91874103-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.176

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTERF1	NM_006980.5	c.691G>A	p.Ala231Thr	missense_variant	3/3	ENST00000351870.8	NP_008911.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTERF1	ENST00000351870.8	c.691G>A	p.Ala231Thr	missense_variant	3/3	1	NM_006980.5	ENSP00000248643.3
MTERF1	ENST00000419292.1	c.631G>A	p.Ala211Thr	missense_variant	2/2	1		ENSP00000414116.1
MTERF1	ENST00000406735.6	c.631G>A	p.Ala211Thr	missense_variant	4/4	2		ENSP00000384986.2
MTERF1	ENST00000454222.5	n.93+5952G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2459 AN: 152108 Hom.: 67 Cov.: 32

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

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

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

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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
LIST_S2	Benign	0.061	.;T;T
MetaRNN	Benign	0.0021	T;T;T
MetaSVM	Benign	-0.96	T
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

Other links and lift over

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