rs6656194

Positions:

• chr1-165795777-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000580248.5(TMCO1):​c.-183+1920G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,182 control chromosomes in the GnomAD database, including 2,104 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (2104 hom., cov: 32)
• Consequence: TMCO1 ENST00000580248.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMCO1	ENST00000580248.5	c.-183+1920G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20651 AN: 152064 Hom.: 2102 Cov.: 32

Gnomad AFR AF: 0.0656

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.146

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.136 AC: 20659 AN: 152182 Hom.: 2104 Cov.: 32 AF XY: 0.141 AC XY: 10457 AN XY: 74398

Gnomad4 AFR AF: 0.0656

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.576

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.144

Alfa AF: 0.132 Hom.: 1384

Bravo AF: 0.135

Asia WGS AF: 0.280 AC: 973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6656194; hg19: chr1-165765014;