12-106985067-A-G

Variant names:

• chr12-106985067-A-G
• rs714359
• NM_001033050.3:c.-58+48T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001033050.3(MTERF2):​c.-58+48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 152,148 control chromosomes in the GnomAD database, including 45,441 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.77 (45406 hom., cov: 31)
  • Exomes 𝑓: 0.85 (35 hom.)
• Consequence: MTERF2 NM_001033050.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 7 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTERF2	NM_001033050.3	c.-58+48T>C		intron_variant	Intron 2 of 2	ENST00000240050.9	NP_001028222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTERF2	ENST00000240050.9	c.-58+48T>C		intron_variant	Intron 2 of 2	1	NM_001033050.3	ENSP00000240050.4

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117043 AN: 151942 Hom.: 45360 Cov.: 31

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.786

GnomAD4 exome AF: 0.852 AC: 75 AN: 88 Hom.: 35 Cov.: 0 AF XY: 0.843 AC XY: 59 AN XY: 70

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 6 AN: 6

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.879 AC: 58 AN: 66

Other (OTH) AF: 0.750 AC: 6 AN: 8

GnomAD4 genome AF: 0.770 AC: 117140 AN: 152060 Hom.: 45406 Cov.: 31 AF XY: 0.774 AC XY: 57518 AN XY: 74320

African (AFR) AF: 0.692 AC: 28705 AN: 41452

American (AMR) AF: 0.845 AC: 12924 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2332 AN: 3470

East Asian (EAS) AF: 0.990 AC: 5119 AN: 5172

South Asian (SAS) AF: 0.811 AC: 3901 AN: 4810

European-Finnish (FIN) AF: 0.776 AC: 8201 AN: 10566

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.787 AC: 53498 AN: 67984

Other (OTH) AF: 0.788 AC: 1662 AN: 2110

Alfa AF: 0.783 Hom.: 76183

Bravo AF: 0.774

Asia WGS AF: 0.894 AC: 3107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.084
DANN	Benign	0.29
PhyloP100		-1.3
PromoterAI		0.0064	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs714359; hg19: chr12-107378845;