dbSNP rs751227407: TMCO1:c.324-14_324-8delTTTTTTT (chr1-165743318-GAAAAAAA-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019026.6(TMCO1):c.324-14_324-8delTTTTTTT variant causes a splice region, intron change. The variant allele was found at a frequency of 0.0000016 in 1,252,592 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: not found (cov: 31)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

TMCO1
NM_019026.6 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.89

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TMCO1	NM_019026.6 link	c.324-14_324-8delTTTTTTT	splice_region_variant, intron_variant	Intron 5 of 6	ENST00000367881.11	NP_061899.3	Q9UM00-1
TMCO1	NM_001256164.1 link	c.375-14_375-8delTTTTTTT	splice_region_variant, intron_variant	Intron 5 of 6		NP_001243093.1	B7Z591
TMCO1	NM_001256165.1 link	c.288-14_288-8delTTTTTTT	splice_region_variant, intron_variant	Intron 5 of 6		NP_001243094.1	B7Z591
TMCO1	NR_045818.1 link	n.418-14_418-8delTTTTTTT	splice_region_variant, intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMCO1	ENST00000367881.11 link	c.324-14_324-8delTTTTTTT		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_019026.6	ENSP00000356856.6		Q9UM00-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000160

AC:

AN:

1252592

Hom.:

AF XY:

0.00000319

AC XY:

AN XY:

627072

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000211

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over