Genetic Variant TMCO1:c.469-141_469-140dupAA (chr1-165728260-C-CTT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_019026.6(TMCO1):c.469-141_469-140dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 462,502 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000049 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0015 ( 0 hom. )

Consequence

TMCO1
NM_019026.6 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.355

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

cerebrofaciothoracic dysplasia
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Illumina, Laboratory for Molecular Medicine, Orphanet
craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

TMCO1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019026.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMCO1	NM_019026.6	MANE Select	c.469-141_469-140dupAA	intron	N/A	NP_061899.3	Q9UM00-1
TMCO1	NM_001256164.1		c.520-141_520-140dupAA	intron	N/A	NP_001243093.1	B7Z591
TMCO1	NM_001256165.1		c.433-141_433-140dupAA	intron	N/A	NP_001243094.1	B7Z591

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMCO1	ENST00000367881.11	TSL:1 MANE Select	c.469-140_469-139insAA	intron	N/A	ENSP00000356856.6	Q9UM00-1
TMCO1	ENST00000612311.4	TSL:1	c.622-140_622-139insAA	intron	N/A	ENSP00000480514.1	Q9UM00-3
TMCO1	ENST00000868463.1		c.592-140_592-139insAA	intron	N/A	ENSP00000538522.1

Frequencies

GnomAD3 genomes

AF:

0.0000485

AC:

AN:

144238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000298

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000765

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00145

AC:

462

AN:

318214

Hom.:

AF XY:

0.00156

AC XY:

277

AN XY:

177320

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00328

AC:

AN:

7934

American (AMR)

AF:

0.000843

AC:

AN:

20156

Ashkenazi Jewish (ASJ)

AF:

0.00284

AC:

AN:

8804

East Asian (EAS)

AF:

0.00160

AC:

AN:

13156

South Asian (SAS)

AF:

0.000701

AC:

AN:

49948

European-Finnish (FIN)

AF:

0.00136

AC:

AN:

16234

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

1156

European-Non Finnish (NFE)

AF:

0.00160

AC:

297

AN:

186114

Other (OTH)

AF:

0.00116

AC:

AN:

14712

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.257

Heterozygous variant carriers

110

165

220

275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000485

AC:

AN:

144288

Hom.:

Cov.:

AF XY:

0.0000857

AC XY:

AN XY:

70006

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

39632

American (AMR)

AF:

0.00

AC:

AN:

14398

Ashkenazi Jewish (ASJ)

AF:

0.000298

AC:

AN:

3354

East Asian (EAS)

AF:

0.00

AC:

AN:

4996

South Asian (SAS)

AF:

0.00

AC:

AN:

4522

European-Finnish (FIN)

AF:

0.000113

AC:

AN:

8878

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.0000765

AC:

AN:

65368

Other (OTH)

AF:

0.00

AC:

AN:

1972

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000406148), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.339

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-165728260-CTTTT-CTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over