1-165728260-C-CT

Position:

• chr1-165728260-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_019026.6(TMCO1):​c.469-140_469-139insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0818 in 436,994 control chromosomes in the GnomAD database, including 73 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (71 hom., cov: 31)
  • Exomes 𝑓: 0.11 (2 hom.)
• Consequence: TMCO1 NM_019026.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.355

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 -10 ACMG points.

• BP6: Variant 1-165728260-C-CT is Benign according to our data. Variant chr1-165728260-C-CT is described in ClinVar as [Benign]. Clinvar id is 1277148.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.052 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMCO1	NM_019026.6	c.469-140_469-139insA		intron_variant		ENST00000367881.11
TMCO1	NM_001256164.1	c.520-140_520-139insA		intron_variant
TMCO1	NM_001256165.1	c.433-140_433-139insA		intron_variant
TMCO1	NR_045818.1	n.563-140_563-139insA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMCO1	ENST00000367881.11	c.469-140_469-139insA		intron_variant		1	NM_019026.6	P1

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3479 AN: 144110 Hom.: 72 Cov.: 31

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0144

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.00485

Gnomad FIN AF: 0.0113

Gnomad MID AF: 0.0395

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.0184

GnomAD4 exome AF: 0.110 AC: 32242 AN: 292834 Hom.: 2 AF XY: 0.111 AC XY: 18029 AN XY: 162998

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.0873

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.0242 AC: 3487 AN: 144160 Hom.: 71 Cov.: 31 AF XY: 0.0231 AC XY: 1614 AN XY: 69938

Gnomad4 AFR AF: 0.0539

Gnomad4 AMR AF: 0.0145

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.0250

Gnomad4 SAS AF: 0.00442

Gnomad4 FIN AF: 0.0113

Gnomad4 NFE AF: 0.0113

Gnomad4 OTH AF: 0.0188

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs397967679; hg19: chr1-165697497;