12-106978047-G-C

Position:

• chr12-106978047-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001033050.3(MTERF2):​c.668C>G​(p.Ser223Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 2.66

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTERF2	NM_001033050.3	c.668C>G	p.Ser223Cys	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.668C>G	p.Ser223Cys	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

Mar 22, 2023

The c.668C>G (p.S223C) alteration is located in exon 3 (coding exon 1) of the MTERF2 gene. This alteration results from a C to G substitution at nucleotide position 668, causing the serine (S) at amino acid position 223 to be replaced by a cysteine (C). 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	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.78	.;.;T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.3	D;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.024	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.33
MutPred		0.70		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.39
MPC		0.33
ClinPred		0.96	D
GERP RS		5.8
Varity_R		0.19
gMVP		0.34

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: chr12-107371825;