chr8-96256964-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_015942.5(MTERF3):c.485T>C(p.Leu162Pro) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00027 in 1,598,420 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00027 ( 0 hom. )
Consequence
MTERF3
NM_015942.5 missense, splice_region
NM_015942.5 missense, splice_region
Scores
9
6
2
Splicing: ADA: 0.7001
1
1
Clinical Significance
Conservation
PhyloP100: 8.65
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTERF3 | NM_015942.5 | c.485T>C | p.Leu162Pro | missense_variant, splice_region_variant | 3/8 | ENST00000287025.4 | |
MTERF3 | NM_001286643.1 | c.485T>C | p.Leu162Pro | missense_variant, splice_region_variant | 3/9 | ||
MTERF3 | XM_011517054.3 | c.146T>C | p.Leu49Pro | missense_variant, splice_region_variant | 3/8 | ||
MTERF3 | NM_001362964.1 | c.-86T>C | splice_region_variant, 5_prime_UTR_variant | 3/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTERF3 | ENST00000287025.4 | c.485T>C | p.Leu162Pro | missense_variant, splice_region_variant | 3/8 | 1 | NM_015942.5 | P1 | |
MTERF3 | ENST00000523821.5 | c.485T>C | p.Leu162Pro | missense_variant, splice_region_variant | 3/9 | 1 | |||
MTERF3 | ENST00000522822.5 | c.122T>C | p.Leu41Pro | missense_variant, splice_region_variant | 1/6 | 2 | |||
MTERF3 | ENST00000524341.5 | c.-86T>C | splice_region_variant, 5_prime_UTR_variant | 1/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000276 AC: 42AN: 152250Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000174 AC: 41AN: 235292Hom.: 0 AF XY: 0.000197 AC XY: 25AN XY: 127072
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GnomAD4 exome AF: 0.000269 AC: 389AN: 1446170Hom.: 0 Cov.: 30 AF XY: 0.000287 AC XY: 206AN XY: 719020
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GnomAD4 genome ? AF: 0.000276 AC: 42AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74382
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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 | Dec 07, 2021 | The c.485T>C (p.L162P) alteration is located in exon 3 (coding exon 2) of the MTERF3 gene. This alteration results from a T to C substitution at nucleotide position 485, causing the leucine (L) at amino acid position 162 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;D
Vest4
MVP
MPC
0.25
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at