chr1-165728057-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_019026.6(TMCO1):āc.533T>Cā(p.Leu178Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,456,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 31)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
TMCO1
NM_019026.6 missense
NM_019026.6 missense
Scores
4
7
6
Clinical Significance
Conservation
PhyloP100: 7.00
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 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 |
---|---|---|---|---|---|---|---|
TMCO1 | NM_019026.6 | c.533T>C | p.Leu178Pro | missense_variant | 7/7 | ENST00000367881.11 | |
TMCO1 | NM_001256164.1 | c.584T>C | p.Leu195Pro | missense_variant | 7/7 | ||
TMCO1 | NM_001256165.1 | c.497T>C | p.Leu166Pro | missense_variant | 7/7 | ||
TMCO1 | NR_045818.1 | n.627T>C | non_coding_transcript_exon_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMCO1 | ENST00000367881.11 | c.533T>C | p.Leu178Pro | missense_variant | 7/7 | 1 | NM_019026.6 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1456884Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2AN XY: 724772
GnomAD4 exome
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AC:
2
AN:
1456884
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Cov.:
31
AF XY:
AC XY:
2
AN XY:
724772
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 17, 2024 | The c.533T>C (p.L178P) alteration is located in exon 7 (coding exon 7) of the TMCO1 gene. This alteration results from a T to C substitution at nucleotide position 533, causing the leucine (L) at amino acid position 178 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
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;.;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;N;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
REVEL
Benign
Sift4G
Uncertain
T;T;T;T;T
Polyphen
0.52
.;P;.;.;.
Vest4
MutPred
0.54
.;Gain of relative solvent accessibility (P = 0.005);.;.;.;
MVP
MPC
1.7
ClinPred
D
GERP RS
Varity_R
gMVP
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
Publications
No publications associated with this variant yet.