1-165770361-C-T

Variant names:

• chr1-165770361-C-T
• rs2814471
• ENST00000580248.5:c.-182-2092G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000580248.5(TMCO1):​c.-182-2092G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 152,206 control chromosomes in the GnomAD database, including 59,389 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 0.88 (59389 hom., cov: 32)
• Consequence: TMCO1 ENST00000580248.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• Publications: 13 publications found

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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.447+986C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMCO1	ENST00000580248.5	c.-182-2092G>A		intron_variant	Intron 3 of 8	2		ENSP00000462588.1
TMCO1-AS1	ENST00000423121.1	n.447+986C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134242 AN: 152088 Hom.: 59343 Cov.: 32

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.938

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.886

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

GnomAD4 genome AF: 0.883 AC: 134347 AN: 152206 Hom.: 59389 Cov.: 32 AF XY: 0.882 AC XY: 65657 AN XY: 74400

African (AFR) AF: 0.887 AC: 36811 AN: 41520

American (AMR) AF: 0.873 AC: 13333 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.926 AC: 3214 AN: 3472

East Asian (EAS) AF: 0.991 AC: 5141 AN: 5188

South Asian (SAS) AF: 0.938 AC: 4525 AN: 4822

European-Finnish (FIN) AF: 0.819 AC: 8668 AN: 10588

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.877 AC: 59675 AN: 68020

Other (OTH) AF: 0.887 AC: 1875 AN: 2114

Alfa AF: 0.880 Hom.: 74601

Bravo AF: 0.885

Asia WGS AF: 0.955 AC: 3320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.40
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2814471; hg19: chr1-165739598;