rs1913845

Positions:

• chr1-165726342-C-T

Variant summary

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

The NM_001256164.1(TMCO1):​c.*1681G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 682,080 control chromosomes in the GnomAD database, including 23,923 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 0.24 (4528 hom., cov: 31)
  • Exomes 𝑓: 0.26 (19395 hom.)
• Consequence: TMCO1 NM_001256164.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMCO1	NM_001256164.1	c.*1681G>A		3_prime_UTR_variant	7/7		NP_001243093.1
TMCO1	NM_001256165.1	c.*1681G>A		3_prime_UTR_variant	7/7		NP_001243094.1
TMCO1	NR_045818.1	n.2342G>A		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMCO1	ENST00000612311	c.*1681G>A		3_prime_UTR_variant	7/7	1		ENSP00000480514.1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36313 AN: 151794 Hom.: 4519 Cov.: 31

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.246

GnomAD3 exomes AF: 0.256 AC: 33351 AN: 130424 Hom.: 4527 AF XY: 0.268 AC XY: 19081 AN XY: 71200

Gnomad AFR exome AF: 0.179

Gnomad AMR exome AF: 0.201

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.141

Gnomad SAS exome AF: 0.357

Gnomad FIN exome AF: 0.205

Gnomad NFE exome AF: 0.281

Gnomad OTH exome AF: 0.249

GnomAD4 exome AF: 0.263 AC: 139576 AN: 530168 Hom.: 19395 Cov.: 0 AF XY: 0.271 AC XY: 77764 AN XY: 287282

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.355

Gnomad4 FIN exome AF: 0.212

Gnomad4 NFE exome AF: 0.277

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.239 AC: 36338 AN: 151912 Hom.: 4528 Cov.: 31 AF XY: 0.237 AC XY: 17630 AN XY: 74248

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.246

Alfa AF: 0.269 Hom.: 7719

Bravo AF: 0.234

Asia WGS AF: 0.256 AC: 888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1913845; hg19: chr1-165695579;