chr1-165728095-GGC-G
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_019026.6(TMCO1):c.493_494del(p.Ala165ProfsTer53) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
TMCO1
NM_019026.6 frameshift
NM_019026.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.50
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 Likely_pathogenic. Variant got 8 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.131 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-165728095-GGC-G is Pathogenic according to our data. Variant chr1-165728095-GGC-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 598949.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMCO1 | NM_019026.6 | c.493_494del | p.Ala165ProfsTer53 | frameshift_variant | 7/7 | ENST00000367881.11 | |
TMCO1 | NM_001256164.1 | c.544_545del | p.Ala182ProfsTer53 | frameshift_variant | 7/7 | ||
TMCO1 | NM_001256165.1 | c.457_458del | p.Ala153ProfsTer53 | frameshift_variant | 7/7 | ||
TMCO1 | NR_045818.1 | n.587_588del | non_coding_transcript_exon_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMCO1 | ENST00000367881.11 | c.493_494del | p.Ala165ProfsTer53 | frameshift_variant | 7/7 | 1 | NM_019026.6 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
See cases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Center for Personalized Medicine, Children's Hospital Los Angeles | Dec 21, 2022 | - - |
Cleft upper lip;C0023529:Periventricular leukomalacia;C0338656:Cognitive impairment;C1850256:Median cleft upper lip;C1858033:Asymmetry of the thorax;C2981150:Cleft palate;C4721788:Bifid ribs Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Center for Personalized Medicine, Children's Hospital Los Angeles | - | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at