Variant 1-165769074-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000580248.5(TMCO1):c.-182-805T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 725,160 control chromosomes in the GnomAD database, including 286,070 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 59358 hom., cov: 31)

Exomes 𝑓: 0.89 ( 226712 hom. )

Consequence

TMCO1
ENST00000580248.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.43

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:

TMCO1-AS1 (HGNC:54046): (TMCO1 antisense RNA 1)

TMCO1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 1-165769074-A-T is Benign according to our data. Variant chr1-165769074-A-T is described in ClinVar as [Benign]. Clinvar id is 1273808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMCO1-AS1	NR_125374.1 link	n.146A>T		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMCO1	ENST00000580248.5 link	c.-182-805T>A		intron_variant	Intron 3 of 8	2		ENSP00000462588.1		J3QQY2
TMCO1-AS1	ENST00000423121.1 link	n.146A>T		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.883

AC:

134192

AN:

152052

Hom.:

59312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.887

Gnomad AMI

AF:

0.913

Gnomad AMR

AF:

0.873

Gnomad ASJ

AF:

0.926

Gnomad EAS

AF:

0.991

Gnomad SAS

AF:

0.937

Gnomad FIN

AF:

0.819

Gnomad MID

AF:

0.930

Gnomad NFE

AF:

0.877

Gnomad OTH

AF:

0.886

GnomAD4 exome

AF:

0.888

AC:

509049

AN:

572990

Hom.:

226712

Cov.:

AF XY:

0.891

AC XY:

264711

AN XY:

297182

show subpopulations

Gnomad4 AFR exome

AF:

0.885

Gnomad4 AMR exome

AF:

0.858

Gnomad4 ASJ exome

AF:

0.918

Gnomad4 EAS exome

AF:

0.996

Gnomad4 SAS exome

AF:

0.936

Gnomad4 FIN exome

AF:

0.815

Gnomad4 NFE exome

AF:

0.879

Gnomad4 OTH exome

AF:

0.889

GnomAD4 genome

AF:

0.883

AC:

134297

AN:

152170

Hom.:

59358

Cov.:

AF XY:

0.882

AC XY:

65643

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.887

Gnomad4 AMR

AF:

0.873

Gnomad4 ASJ

AF:

0.926

Gnomad4 EAS

AF:

0.991

Gnomad4 SAS

AF:

0.938

Gnomad4 FIN

AF:

0.819

Gnomad4 NFE

AF:

0.877

Gnomad4 OTH

AF:

0.887

Alfa

AF:

0.843

Hom.:

2606

Bravo

AF:

0.885

Asia WGS

AF:

0.955

AC:

3320

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.14

DANN

Benign

0.59

Splicing

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