rs12821586

Positions:

• chr12-106986674-G-A
• chr12-106986674-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000552029.1(MTERF2):​c.-1617C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0482 in 152,266 control chromosomes in the GnomAD database, including 226 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 0.048 (226 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MTERF2 ENST00000552029.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTERF2	NM_001033050.3	c.-169+295C>T		intron_variant		ENST00000240050.9	NP_001028222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTERF2	ENST00000240050.9	c.-169+295C>T		intron_variant		1	NM_001033050.3	ENSP00000240050	P1

Frequencies

GnomAD3 genomes AF: 0.0483 AC: 7342 AN: 152150 Hom.: 226 Cov.: 32

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0270

Gnomad ASJ AF: 0.0666

Gnomad EAS AF: 0.0353

Gnomad SAS AF: 0.0799

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0633

Gnomad OTH AF: 0.0411

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 18

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0482 AC: 7335 AN: 152266 Hom.: 226 Cov.: 32 AF XY: 0.0497 AC XY: 3703 AN XY: 74434

Gnomad4 AFR AF: 0.0111

Gnomad4 AMR AF: 0.0269

Gnomad4 ASJ AF: 0.0666

Gnomad4 EAS AF: 0.0352

Gnomad4 SAS AF: 0.0794

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.0633

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0605 Hom.: 150

Bravo AF: 0.0383

Asia WGS AF: 0.0670 AC: 231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.55

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

LitVar

Other links and lift over

dbSNP: rs12821586; hg19: chr12-107380452;