7-91874015-C-G

Variant names:

• chr7-91874015-C-G
• rs530927148
• NM_006980.5:c.779G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006980.5(MTERF1):​c.779G>C​(p.Arg260Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: MTERF1 NM_006980.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13008544).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTERF1	NM_006980.5	MANE Select	c.779G>C	p.Arg260Pro	missense	Exon 3 of 3	NP_008911.1	Q99551
	MTERF1	NM_001301134.2		c.719G>C	p.Arg240Pro	missense	Exon 2 of 2	NP_001288063.1	B4DPR9
	MTERF1	NM_001301135.2		c.719G>C	p.Arg240Pro	missense	Exon 4 of 4	NP_001288064.1	B4DPR9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTERF1	ENST00000351870.8	TSL:1 MANE Select	c.779G>C	p.Arg260Pro	missense	Exon 3 of 3	ENSP00000248643.3	Q99551
	MTERF1	ENST00000419292.1	TSL:1	c.719G>C	p.Arg240Pro	missense	Exon 2 of 2	ENSP00000414116.1	B4DPR9
	MTERF1	ENST00000867199.1		c.779G>C	p.Arg260Pro	missense	Exon 3 of 3	ENSP00000537258.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152062 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD2 exomes AF: 0.0000519 AC: 13 AN: 250690 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000377

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.0000123 AC: 18 AN: 1461776 Hom.: 0 Cov.: 34 AF XY: 0.00000825 AC XY: 6 AN XY: 727190

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000403 AC: 18 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152062 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74270

African (AFR) AF: 0.00 AC: 0 AN: 41396

American (AMR) AF: 0.000131 AC: 2 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000480 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000577 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.3
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.12
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.063	T
Polyphen		0.57	P
Vest4		0.30
MutPred		0.67		Loss of MoRF binding (P = 0.0149)
MVP		0.25
MPC		0.015
ClinPred		0.16	T
GERP RS		4.8
Varity_R		0.88
gMVP		0.82
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs530927148; hg19: chr7-91503329;