chr1-165728057-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019026.6(TMCO1):ā€‹c.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

Scores

4
7
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.00
Variant links:
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]

Genome browser will be placed here

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
TMCO1NM_019026.6 linkuse as main transcriptc.533T>C p.Leu178Pro missense_variant 7/7 ENST00000367881.11
TMCO1NM_001256164.1 linkuse as main transcriptc.584T>C p.Leu195Pro missense_variant 7/7
TMCO1NM_001256165.1 linkuse as main transcriptc.497T>C p.Leu166Pro missense_variant 7/7
TMCO1NR_045818.1 linkuse as main transcriptn.627T>C non_coding_transcript_exon_variant 7/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TMCO1ENST00000367881.11 linkuse as main transcriptc.533T>C p.Leu178Pro missense_variant 7/71 NM_019026.6 P1Q9UM00-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1456884
Hom.:
0
Cov.:
31
AF XY:
0.00000276
AC XY:
2
AN XY:
724772
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
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 submitterclinical testingAmbry GeneticsFeb 17, 2024The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.75
BayesDel_addAF
Pathogenic
0.36
D
BayesDel_noAF
Pathogenic
0.28
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.018
.;T;.;.;.
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.93
D;D;.;.;D
M_CAP
Benign
0.0090
T
MetaRNN
Uncertain
0.64
D;D;D;D;D
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.41
.;N;.;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.80
D
REVEL
Benign
0.26
Sift4G
Uncertain
0.058
T;T;T;T;T
Polyphen
0.52
.;P;.;.;.
Vest4
0.73
MutPred
0.54
.;Gain of relative solvent accessibility (P = 0.005);.;.;.;
MVP
0.29
MPC
1.7
ClinPred
0.95
D
GERP RS
5.4
Varity_R
0.33
gMVP
0.88

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-165697294; API