rs2269811

Variant names:

• chr7-91880237-T-A
• rs2269811
• ENST00000425936.1:c.-214A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-91880237-T-A
• chr7-91880237-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000425936.1(MTERF1):​c.-214A>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 0.00000183 in 545,932 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: MTERF1 ENST00000425936.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 12 publications found

Genes affected

MTERF1 (HGNC:21463): (mitochondrial transcription termination factor 1) This gene encodes a mitochondrial transcription termination factor. This protein participates in attenuating transcription from the mitochondrial genome; this attenuation allows higher levels of expression of 16S ribosomal RNA relative to the tRNA gene downstream. The product of this gene has three leucine zipper motifs bracketed by two basic domains that are all required for DNA binding. There is evidence that, for this protein, the zippers participate in intramolecular interactions that establish the three-dimensional structure required for DNA binding. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000425936.1. 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
	MTERF1	NM_006980.5	MANE Select	c.-30-124A>T		intron	N/A	NP_008911.1	Q99551
	MTERF1	NM_001301134.2		c.-32+420A>T		intron	N/A	NP_001288063.1	B4DPR9
	MTERF1	NM_001301135.2		c.-191-124A>T		intron	N/A	NP_001288064.1	B4DPR9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTERF1	ENST00000425936.1	TSL:1	c.-214A>T		5_prime_UTR	Exon 1 of 2	ENSP00000400966.1	C9JU79
	MTERF1	ENST00000351870.8	TSL:1 MANE Select	c.-30-124A>T		intron	N/A	ENSP00000248643.3	Q99551
	MTERF1	ENST00000419292.1	TSL:1	c.-32+420A>T		intron	N/A	ENSP00000414116.1	B4DPR9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000183 AC: 1 AN: 545932 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 287144

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 14316

American (AMR) AF: 0.00 AC: 0 AN: 19280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14730

East Asian (EAS) AF: 0.00 AC: 0 AN: 31814

South Asian (SAS) AF: 0.00 AC: 0 AN: 48102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3030

European-Non Finnish (NFE) AF: 0.00000283 AC: 1 AN: 353428

Other (OTH) AF: 0.00 AC: 0 AN: 29270

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 3246

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.9
DANN	Benign	0.59
PhyloP100		-1.5
PromoterAI		0.040	Neutral

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: rs2269811; hg19: chr7-91509551;