1-165769226-G-C

Position:

• chr1-165769226-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NR_125374.1(TMCO1-AS1):​n.298G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 411,412 control chromosomes in the GnomAD database, including 164,907 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (60877 hom., cov: 32)
  • Exomes 𝑓: 0.89 (104030 hom.)
• Consequence: TMCO1-AS1 NR_125374.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.716

Genes affected

TMCO1-AS1 (HGNC:54046): (TMCO1 antisense RNA 1)

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-165769226-G-C is Benign according to our data. Variant chr1-165769226-G-C is described in ClinVar as [Benign]. Clinvar id is 1249912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMCO1-AS1	NR_125374.1	n.298G>C		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMCO1-AS1	ENST00000423121.1	n.298G>C		non_coding_transcript_exon_variant	1/2	2
TMCO1	ENST00000580248.5	c.-182-957C>G		intron_variant		2		ENSP00000462588

Frequencies

GnomAD3 genomes AF: 0.894 AC: 135858 AN: 152040 Hom.: 60819 Cov.: 32

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.938

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.895

GnomAD4 exome AF: 0.894 AC: 231898 AN: 259254 Hom.: 104030 Cov.: 2 AF XY: 0.897 AC XY: 122997 AN XY: 137092

Gnomad4 AFR exome AF: 0.932

Gnomad4 AMR exome AF: 0.858

Gnomad4 ASJ exome AF: 0.917

Gnomad4 EAS exome AF: 0.996

Gnomad4 SAS exome AF: 0.937

Gnomad4 FIN exome AF: 0.817

Gnomad4 NFE exome AF: 0.880

Gnomad4 OTH exome AF: 0.893

GnomAD4 genome AF: 0.894 AC: 135976 AN: 152158 Hom.: 60877 Cov.: 32 AF XY: 0.893 AC XY: 66418 AN XY: 74370

Gnomad4 AFR AF: 0.925

Gnomad4 AMR AF: 0.878

Gnomad4 ASJ AF: 0.926

Gnomad4 EAS AF: 0.991

Gnomad4 SAS AF: 0.938

Gnomad4 FIN AF: 0.818

Gnomad4 NFE AF: 0.877

Gnomad4 OTH AF: 0.896

Alfa AF: 0.881 Hom.: 7326

Bravo AF: 0.898

Asia WGS AF: 0.960 AC: 3337 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2790052; hg19: chr1-165738463;