12-106977770-C-G

Position:

• chr12-106977770-C-G

Variant summary

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

The NM_001033050.3(MTERF2):​c.945G>C​(p.Gln315His) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MTERF2 NM_001033050.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0440

Genes affected

MTERF2 (HGNC:30779): (mitochondrial transcription termination factor 2) Enables DNA binding activity. Predicted to be involved in termination of mitochondrial transcription. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

TMEM263 (HGNC:):

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=0.334643).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTERF2	NM_001033050.3	c.945G>C	p.Gln315His	missense_variant	3/3	ENST00000240050.9	NP_001028222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTERF2	ENST00000240050.9	c.945G>C	p.Gln315His	missense_variant	3/3	1	NM_001033050.3	ENSP00000240050.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Jan 26, 2022

The c.945G>C (p.Q315H) alteration is located in exon 3 (coding exon 1) of the MTERF2 gene. This alteration results from a G to C substitution at nucleotide position 945, causing the glutamine (Q) at amino acid position 315 to be replaced by a histidine (H). 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	Pathogenic	0.68
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.30	T;T;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.87	.;.;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-4.3	D;D;D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.41	B;B;B
Vest4		0.34
MutPred		0.69		Loss of stability (P = 0.161);Loss of stability (P = 0.161);Loss of stability (P = 0.161);
MVP		0.14
MPC		0.33
ClinPred		0.99	D
GERP RS		0.55
Varity_R		0.75
gMVP		0.77

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: chr12-107371548;