chr1-165728260-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_019026.6(TMCO1):​c.469-140_469-139insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0818 in 436,994 control chromosomes in the GnomAD database, including 73 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.024 ( 71 hom., cov: 31)
Exomes 𝑓: 0.11 ( 2 hom. )

Consequence

TMCO1
NM_019026.6 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.355
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 Benign. Variant got -10 ACMG points.

BP6
Variant 1-165728260-C-CT is Benign according to our data. Variant chr1-165728260-C-CT is described in ClinVar as [Benign]. Clinvar id is 1277148.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.052 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TMCO1NM_019026.6 linkuse as main transcriptc.469-140_469-139insA intron_variant ENST00000367881.11
TMCO1NM_001256164.1 linkuse as main transcriptc.520-140_520-139insA intron_variant
TMCO1NM_001256165.1 linkuse as main transcriptc.433-140_433-139insA intron_variant
TMCO1NR_045818.1 linkuse as main transcriptn.563-140_563-139insA intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TMCO1ENST00000367881.11 linkuse as main transcriptc.469-140_469-139insA intron_variant 1 NM_019026.6 P1Q9UM00-1

Frequencies

GnomAD3 genomes
AF:
0.0241
AC:
3479
AN:
144110
Hom.:
72
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0538
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0144
Gnomad ASJ
AF:
0.0334
Gnomad EAS
AF:
0.0254
Gnomad SAS
AF:
0.00485
Gnomad FIN
AF:
0.0113
Gnomad MID
AF:
0.0395
Gnomad NFE
AF:
0.0112
Gnomad OTH
AF:
0.0184
GnomAD4 exome
AF:
0.110
AC:
32242
AN:
292834
Hom.:
2
AF XY:
0.111
AC XY:
18029
AN XY:
162998
show subpopulations
Gnomad4 AFR exome
AF:
0.145
Gnomad4 AMR exome
AF:
0.103
Gnomad4 ASJ exome
AF:
0.122
Gnomad4 EAS exome
AF:
0.106
Gnomad4 SAS exome
AF:
0.108
Gnomad4 FIN exome
AF:
0.0873
Gnomad4 NFE exome
AF:
0.111
Gnomad4 OTH exome
AF:
0.114
GnomAD4 genome
AF:
0.0242
AC:
3487
AN:
144160
Hom.:
71
Cov.:
31
AF XY:
0.0231
AC XY:
1614
AN XY:
69938
show subpopulations
Gnomad4 AFR
AF:
0.0539
Gnomad4 AMR
AF:
0.0145
Gnomad4 ASJ
AF:
0.0334
Gnomad4 EAS
AF:
0.0250
Gnomad4 SAS
AF:
0.00442
Gnomad4 FIN
AF:
0.0113
Gnomad4 NFE
AF:
0.0113
Gnomad4 OTH
AF:
0.0188

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxAug 21, 2019- -

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: rs397967679; hg19: chr1-165697497; API