1-165769226-G-C

Variant names:

• chr1-165769226-G-C
• rs2790052
• ENST00000580248.5:c.-182-957C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000580248.5(TMCO1):​c.-182-957C>G variant causes a intron 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 ENST00000580248.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.716

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMCO1-AS1	NR_125374.1	n.298G>C		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMCO1	ENST00000580248.5	c.-182-957C>G		intron_variant	Intron 3 of 8	2		ENSP00000462588.1
TMCO1-AS1	ENST00000423121.1	n.298G>C		non_coding_transcript_exon_variant	Exon 1 of 2	2

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 AC: 7481 AN: 8028

Gnomad4 AMR exome AF: 0.858 AC: 9774 AN: 11390

Gnomad4 ASJ exome AF: 0.917 AC: 7100 AN: 7744

Gnomad4 EAS exome AF: 0.996 AC: 14531 AN: 14586

Gnomad4 SAS exome AF: 0.937 AC: 34470 AN: 36798

Gnomad4 FIN exome AF: 0.817 AC: 10237 AN: 12532

Gnomad4 NFE exome AF: 0.880 AC: 134357 AN: 152598

Gnomad4 Remaining exome AF: 0.893 AC: 12945 AN: 14498

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 AC: 0.924758 AN: 0.924758

Gnomad4 AMR AF: 0.878 AC: 0.878336 AN: 0.878336

Gnomad4 ASJ AF: 0.926 AC: 0.925691 AN: 0.925691

Gnomad4 EAS AF: 0.991 AC: 0.990916 AN: 0.990916

Gnomad4 SAS AF: 0.938 AC: 0.938226 AN: 0.938226

Gnomad4 FIN AF: 0.818 AC: 0.818285 AN: 0.818285

Gnomad4 NFE AF: 0.877 AC: 0.877125 AN: 0.877125

Gnomad4 OTH AF: 0.896 AC: 0.896209 AN: 0.896209

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 31, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.59
Mutation Taster		=100/0	polymorphism (auto)

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;