rs1057517698
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_181783.4(TMTC3):c.3G>A(p.Met1?) variant causes a start lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
TMTC3
NM_181783.4 start_lost
NM_181783.4 start_lost
Scores
4
8
4
Clinical Significance
Conservation
PhyloP100: 8.69
Genes affected
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 12-88148318-G-A is Pathogenic according to our data. Variant chr12-88148318-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 372277.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMTC3 | NM_181783.4 | c.3G>A | p.Met1? | start_lost | 2/14 | ENST00000266712.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMTC3 | ENST00000266712.11 | c.3G>A | p.Met1? | start_lost | 2/14 | 1 | NM_181783.4 | P1 | |
TMTC3 | ENST00000547034.5 | c.3G>A | p.Met1? | start_lost, NMD_transcript_variant | 2/12 | 1 | |||
TMTC3 | ENST00000549011.5 | c.3G>A | p.Met1? | start_lost | 2/4 | 4 | |||
TMTC3 | ENST00000551088.1 | c.3G>A | p.Met1? | start_lost | 2/5 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Lissencephaly 8 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 17, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
0.42
.;B;.
Vest4
0.96
MutPred
Gain of catalytic residue at L6 (P = 0.0017);Gain of catalytic residue at L6 (P = 0.0017);Gain of catalytic residue at L6 (P = 0.0017);
MVP
ClinPred
D
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: -30
Find out detailed SpliceAI scores and Pangolin per-transcript scores at