NM_001033050.3:c.945G>C

Variant names:

• chr12-106977770-C-G
• rs1952001723
• NM_001033050.3:c.945G>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q315R) has been classified 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
• Publications: 0 publications found

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:28281): (transmembrane protein 263) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.334643).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033050.3. 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
	MTERF2	NM_001033050.3	MANE Select	c.945G>C	p.Gln315His	missense	Exon 3 of 3	NP_001028222.1	Q49AM1
	MTERF2	NM_025198.5		c.945G>C	p.Gln315His	missense	Exon 3 of 3	NP_079474.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTERF2	ENST00000240050.9	TSL:1 MANE Select	c.945G>C	p.Gln315His	missense	Exon 3 of 3	ENSP00000240050.4	Q49AM1
	MTERF2	ENST00000392830.6	TSL:1	c.945G>C	p.Gln315His	missense	Exon 3 of 3	ENSP00000376575.2	Q49AM1
	MTERF2	ENST00000552029.1	TSL:1	c.945G>C	p.Gln315His	missense	Exon 2 of 2	ENSP00000447651.1	Q49AM1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	0.68
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.30	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
MetaSVM	Benign	-1.1	T
PhyloP100		0.044
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.41	B
Vest4		0.34
MutPred		0.69		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
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs1952001723; hg19: chr12-107371548;