Variant 1-165728104-G-A details in Genebe, Genetics Data Aggregator

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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

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]

TMCO1 links:

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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
TMCO1	NM_019026.6 linkuse as main transcript	c.486C>T	p.Leu162=	synonymous_variant	7/7	ENST00000367881.11
TMCO1	NM_001256164.1 linkuse as main transcript	c.537C>T	p.Leu179=	synonymous_variant	7/7
TMCO1	NM_001256165.1 linkuse as main transcript	c.450C>T	p.Leu150=	synonymous_variant	7/7
TMCO1	NR_045818.1 linkuse as main transcript	n.580C>T		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMCO1	ENST00000367881.11 linkuse as main transcript	c.486C>T	p.Leu162=	synonymous_variant	7/7	1	NM_019026.6	P1	Q9UM00-1

Frequencies

GnomAD3 genomes

AF:

0.0290

AC:

4412

AN:

152134

Hom.:

107

Cov.:

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.:

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.:

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.:

Bravo

AF:

0.0316

Asia WGS

AF:

0.00866

AC:

AN:

3478

EpiCase

AF:

0.0436

EpiControl

AF:

0.0388

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over