1-165728095-GGC-G

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_494delGC​(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

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.50
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]

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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 rank MANE Protein UniProt
TMCO1NM_019026.6 linkc.493_494delGC p.Ala165ProfsTer53 frameshift_variant Exon 7 of 7 ENST00000367881.11 NP_061899.3 Q9UM00-1
TMCO1NM_001256164.1 linkc.544_545delGC p.Ala182ProfsTer53 frameshift_variant Exon 7 of 7 NP_001243093.1 B7Z591
TMCO1NM_001256165.1 linkc.457_458delGC p.Ala153ProfsTer53 frameshift_variant Exon 7 of 7 NP_001243094.1 B7Z591
TMCO1NR_045818.1 linkn.587_588delGC non_coding_transcript_exon_variant Exon 7 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMCO1ENST00000367881.11 linkc.493_494delGC p.Ala165ProfsTer53 frameshift_variant Exon 7 of 7 1 NM_019026.6 ENSP00000356856.6 Q9UM00-1

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

HP:0000161 (present);na:HP:0000175 (present);na:HP:0000204 (present);na:HP:0000892 (present);na:HP:0001555 (present);na:HP:0006970 (present);na:HP:0100543 (present) Pathogenic:1
Nov 19, 2018
Center for Personalized Medicine, Children's Hospital Los Angeles
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1558027212; hg19: chr1-165697332; API