7-91873896-G-C

Position:

• chr7-91873896-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006980.5(MTERF1):​c.898C>G​(p.Leu300Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTERF1 NM_006980.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.83

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38215807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTERF1	NM_006980.5	c.898C>G	p.Leu300Val	missense_variant	3/3	ENST00000351870.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTERF1	ENST00000351870.8	c.898C>G	p.Leu300Val	missense_variant	3/3	1	NM_006980.5
MTERF1	ENST00000419292.1	c.838C>G	p.Leu280Val	missense_variant	2/2	1		P1
MTERF1	ENST00000406735.6	c.838C>G	p.Leu280Val	missense_variant	4/4	2		P1
MTERF1	ENST00000454222.5	n.93+6159C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 02, 2022

The c.898C>G (p.L300V) alteration is located in exon 3 (coding exon 2) of the MTERF1 gene. This alteration results from a C to G substitution at nucleotide position 898, causing the leucine (L) at amino acid position 300 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T;T;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.38	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.98	D;D;D
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.91	N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.011	D;D;D
Sift4G	Uncertain	0.012	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.30
MutPred		0.74		.;Gain of sheet (P = 0.0221);.;
MVP		0.52
MPC		0.11
ClinPred		0.83	D
GERP RS		4.9
Varity_R		0.21
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-91503210;