chr1-165768763-GTC-G
Position:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The ENST00000612311.4(TMCO1):c.140_141del(p.Arg47ThrfsTer52) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Consequence
TMCO1
ENST00000612311.4 frameshift
ENST00000612311.4 frameshift
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.124
Genes affected
TMCO1 (HGNC:18188): (transmembrane and coiled-coil domains 1) This locus encodes a transmembrane protein. Mutations at this locus have been associated with craniofacial dysmorphism, skeletal anomalies, and cognitive disability. Mutations at this locus have also been associated with open angle glaucoma blindness. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMCO1 | NM_019026.6 | c.-14_-13del | 5_prime_UTR_variant | 1/7 | ENST00000367881.11 | ||
TMCO1 | NM_001256164.1 | c.140_141del | p.Arg47ThrfsTer18 | frameshift_variant | 1/7 | ||
TMCO1 | NM_001256165.1 | c.-250_-249del | 5_prime_UTR_variant | 1/7 | |||
TMCO1 | NR_045818.1 | n.158_159del | non_coding_transcript_exon_variant | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMCO1 | ENST00000367881.11 | c.-14_-13del | 5_prime_UTR_variant | 1/7 | 1 | NM_019026.6 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at