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GeneBe

1-165728104-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_019026.6(TMCO1):c.486C>T(p.Leu162=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0354 in 1,607,392 control chromosomes in the GnomAD database, including 1,221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 107 hom., cov: 32)
Exomes 𝑓: 0.036 ( 1114 hom. )

Consequence

TMCO1
NM_019026.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.980
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 -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 1-165728104-G-A is Benign according to our data. Variant chr1-165728104-G-A is described in ClinVar as [Benign]. Clinvar id is 1235043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.98 with no splicing effect.
BA1
GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0667 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TMCO1NM_019026.6 linkuse as main transcriptc.486C>T p.Leu162= synonymous_variant 7/7 ENST00000367881.11
TMCO1NM_001256164.1 linkuse as main transcriptc.537C>T p.Leu179= synonymous_variant 7/7
TMCO1NM_001256165.1 linkuse as main transcriptc.450C>T p.Leu150= synonymous_variant 7/7
TMCO1NR_045818.1 linkuse as main transcriptn.580C>T 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.486C>T p.Leu162= synonymous_variant 7/71 NM_019026.6 P1Q9UM00-1

Frequencies

GnomAD3 genomes
AF:
0.0290
AC:
4412
AN:
152134
Hom.:
107
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00625
Gnomad AMI
AF:
0.111
Gnomad AMR
AF:
0.0503
Gnomad ASJ
AF:
0.0199
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.0137
Gnomad FIN
AF:
0.0247
Gnomad MID
AF:
0.0570
Gnomad NFE
AF:
0.0412
Gnomad OTH
AF:
0.0316
GnomAD3 exomes
AF:
0.0338
AC:
8489
AN:
250914
Hom.:
208
AF XY:
0.0331
AC XY:
4489
AN XY:
135684
show subpopulations
Gnomad AFR exome
AF:
0.00486
Gnomad AMR exome
AF:
0.0695
Gnomad ASJ exome
AF:
0.0169
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.0162
Gnomad FIN exome
AF:
0.0268
Gnomad NFE exome
AF:
0.0404
Gnomad OTH exome
AF:
0.0300
GnomAD4 exome
AF:
0.0361
AC:
52521
AN:
1455140
Hom.:
1114
Cov.:
31
AF XY:
0.0357
AC XY:
25852
AN XY:
723894
show subpopulations
Gnomad4 AFR exome
AF:
0.00546
Gnomad4 AMR exome
AF:
0.0688
Gnomad4 ASJ exome
AF:
0.0162
Gnomad4 EAS exome
AF:
0.000127
Gnomad4 SAS exome
AF:
0.0160
Gnomad4 FIN exome
AF:
0.0277
Gnomad4 NFE exome
AF:
0.0398
Gnomad4 OTH exome
AF:
0.0305
GnomAD4 genome
AF:
0.0290
AC:
4421
AN:
152252
Hom.:
107
Cov.:
32
AF XY:
0.0280
AC XY:
2087
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.00623
Gnomad4 AMR
AF:
0.0508
Gnomad4 ASJ
AF:
0.0199
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.0137
Gnomad4 FIN
AF:
0.0247
Gnomad4 NFE
AF:
0.0412
Gnomad4 OTH
AF:
0.0313
Alfa
AF:
0.0344
Hom.:
45
Bravo
AF:
0.0316
Asia WGS
AF:
0.00866
AC:
31
AN:
3478
EpiCase
AF:
0.0436
EpiControl
AF:
0.0388

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxNov 15, 2018- -
Benign, criteria provided, single submitterclinical testingInvitaeJan 28, 2024- -
Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 10, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
Cadd
Benign
5.7
Dann
Benign
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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: rs78363884; hg19: chr1-165697341; API