Genetic Variant TMCO1:c.324-8_324-7insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT (chr1-165743318-G-GAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA) – 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.324-8_324-7insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000798 in 1,252,594 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

TMCO1
NM_019026.6 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.01

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:

Genome browser will be placed here

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.324-8_324-7insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT	splice_region intron	N/A	NP_061899.3	Q9UM00-1
TMCO1	NM_001256164.1		c.375-8_375-7insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT	splice_region intron	N/A	NP_001243093.1	B7Z591
TMCO1	NM_001256165.1		c.288-8_288-7insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT	splice_region 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.324-8_324-7insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT	splice_region intron	N/A	ENSP00000356856.6	Q9UM00-1
TMCO1	ENST00000612311.4	TSL:1	c.477-8_477-7insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT	splice_region intron	N/A	ENSP00000480514.1	Q9UM00-3
TMCO1	ENST00000868463.1		c.447-8_447-7insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT	splice_region intron	N/A	ENSP00000538522.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.98e-7

AC:

AN:

1252594

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

627072

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27894

American (AMR)

AF:

0.00

AC:

AN:

37084

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22992

East Asian (EAS)

AF:

0.00

AC:

AN:

35862

South Asian (SAS)

AF:

0.00

AC:

AN:

75188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48122

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4346

European-Non Finnish (NFE)

AF:

0.00000105

AC:

AN:

948838

Other (OTH)

AF:

0.00

AC:

AN:

52268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.0

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.

1-165743318-GAAAAAAA-GAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over