8-96245912-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_015942.5(MTERF3):c.845G>A(p.Arg282His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
MTERF3
NM_015942.5 missense
NM_015942.5 missense
Scores
1
7
10
Clinical Significance
Conservation
PhyloP100: 2.98
Genes affected
MTERF3 (HGNC:24258): (mitochondrial transcription termination factor 3) Enables transcription cis-regulatory region binding activity. Involved in negative regulation of transcription, DNA-templated. Located in cytosol and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36061907).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MTERF3 | NM_015942.5 | c.845G>A | p.Arg282His | missense_variant | 6/8 | ENST00000287025.4 | NP_057026.3 | |
MTERF3 | NM_001286643.1 | c.845G>A | p.Arg282His | missense_variant | 6/9 | NP_001273572.1 | ||
MTERF3 | NM_001362964.1 | c.275G>A | p.Arg92His | missense_variant | 6/8 | NP_001349893.1 | ||
MTERF3 | XM_011517054.3 | c.506G>A | p.Arg169His | missense_variant | 6/8 | XP_011515356.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MTERF3 | ENST00000287025.4 | c.845G>A | p.Arg282His | missense_variant | 6/8 | 1 | NM_015942.5 | ENSP00000287025 | P1 | |
MTERF3 | ENST00000523821.5 | c.845G>A | p.Arg282His | missense_variant | 6/9 | 1 | ENSP00000429400 | |||
MTERF3 | ENST00000522822.5 | c.482G>A | p.Arg161His | missense_variant | 4/6 | 2 | ENSP00000430138 | |||
MTERF3 | ENST00000524341.5 | c.275G>A | p.Arg92His | missense_variant | 4/5 | 3 | ENSP00000429267 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152106Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251326Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135836
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GnomAD4 exome AF: 0.0000356 AC: 52AN: 1461644Hom.: 0 Cov.: 30 AF XY: 0.0000316 AC XY: 23AN XY: 727108
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152106Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74312
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 04, 2023 | The c.845G>A (p.R282H) alteration is located in exon 6 (coding exon 5) of the MTERF3 gene. This alteration results from a G to A substitution at nucleotide position 845, causing the arginine (R) at amino acid position 282 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;T;T;D
Polyphen
D;.;.;P
Vest4
MutPred
Loss of MoRF binding (P = 0.0076);.;.;Loss of MoRF binding (P = 0.0076);
MVP
MPC
0.035
ClinPred
D
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at