Variant chr1-165752181-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_019026.6(TMCO1):c.256-12G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00787 in 1,606,824 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 6 hom., cov: 31)

Exomes 𝑓: 0.0081 ( 63 hom. )

Consequence

TMCO1
NM_019026.6 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004043

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.697

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-165752181-C-T is Benign according to our data. Variant chr1-165752181-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1198076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
TMCO1	NM_019026.6 linkuse as main transcript	c.256-12G>A	splice_polypyrimidine_tract_variant, intron_variant	ENST00000367881.11
TMCO1	NM_001256164.1 linkuse as main transcript	c.307-12G>A	splice_polypyrimidine_tract_variant, intron_variant
TMCO1	NM_001256165.1 linkuse as main transcript	c.220-12G>A	splice_polypyrimidine_tract_variant, intron_variant
TMCO1	NR_045818.1 linkuse as main transcript	n.350-12G>A	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMCO1	ENST00000367881.11 linkuse as main transcript	c.256-12G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_019026.6	P1	Q9UM00-1

Frequencies

GnomAD3 genomes

AF:

0.00554

AC:

831

AN:

150114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00160

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00266

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000976

Gnomad SAS

AF:

0.00292

Gnomad FIN

AF:

0.00222

Gnomad MID

AF:

0.00968

Gnomad NFE

AF:

0.00999

Gnomad OTH

AF:

0.00242

GnomAD3 exomes

AF:

0.00534

AC:

1339

AN:

250562

Hom.:

AF XY:

0.00537

AC XY:

728

AN XY:

135442

show subpopulations

Gnomad AFR exome

AF:

0.00136

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00125

Gnomad SAS exome

AF:

0.00407

Gnomad FIN exome

AF:

0.00296

Gnomad NFE exome

AF:

0.00865

Gnomad OTH exome

AF:

0.00507

GnomAD4 exome

AF:

0.00811

AC:

11818

AN:

1456654

Hom.:

Cov.:

AF XY:

0.00794

AC XY:

5754

AN XY:

724900

show subpopulations

Gnomad4 AFR exome

AF:

0.00153

Gnomad4 AMR exome

AF:

0.00257

Gnomad4 ASJ exome

AF:

0.000345

Gnomad4 EAS exome

AF:

0.000455

Gnomad4 SAS exome

AF:

0.00477

Gnomad4 FIN exome

AF:

0.00332

Gnomad4 NFE exome

AF:

0.00959

Gnomad4 OTH exome

AF:

0.00661

GnomAD4 genome

AF:

0.00552

AC:

829

AN:

150170

Hom.:

Cov.:

AF XY:

0.00511

AC XY:

374

AN XY:

73162

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.00259

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000979

Gnomad4 SAS

AF:

0.00293

Gnomad4 FIN

AF:

0.00222

Gnomad4 NFE

AF:

0.00997

Gnomad4 OTH

AF:

0.00240

Alfa

AF:

0.00731

Hom.:

Bravo

AF:

0.00531

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign/Likely 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 submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 18, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 12, 2021	- -

Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.6

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000040

dbscSNV1_RF

Benign

0.0

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.

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