1-165751986-T-C

Position:

• chr1-165751986-T-C

Variant summary

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

The NM_019026.6(TMCO1):​c.323+116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 838,792 control chromosomes in the GnomAD database, including 135,514 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21532 hom., cov: 31)
  • Exomes 𝑓: 0.57 (113982 hom.)
• Consequence: TMCO1 NM_019026.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0580

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-165751986-T-C is Benign according to our data. Variant chr1-165751986-T-C is described in ClinVar as [Benign]. Clinvar id is 1283707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMCO1	NM_019026.6	c.323+116A>G		intron_variant		ENST00000367881.11
TMCO1	NM_001256164.1	c.374+116A>G		intron_variant
TMCO1	NM_001256165.1	c.287+116A>G		intron_variant
TMCO1	NR_045818.1	n.417+116A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMCO1	ENST00000367881.11	c.323+116A>G		intron_variant		1	NM_019026.6	P1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79680 AN: 151772 Hom.: 21512 Cov.: 31

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.535

GnomAD4 exome AF: 0.569 AC: 391173 AN: 686900 Hom.: 113982 AF XY: 0.578 AC XY: 209089 AN XY: 361466

Gnomad4 AFR exome AF: 0.419

Gnomad4 AMR exome AF: 0.491

Gnomad4 ASJ exome AF: 0.601

Gnomad4 EAS exome AF: 0.346

Gnomad4 SAS exome AF: 0.739

Gnomad4 FIN exome AF: 0.474

Gnomad4 NFE exome AF: 0.582

Gnomad4 OTH exome AF: 0.568

GnomAD4 genome AF: 0.525 AC: 79739 AN: 151892 Hom.: 21532 Cov.: 31 AF XY: 0.524 AC XY: 38899 AN XY: 74226

Gnomad4 AFR AF: 0.420

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.541

Alfa AF: 0.538 Hom.: 2874

Bravo AF: 0.516

Asia WGS AF: 0.583 AC: 2024 AN: 3470

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	-0.83
CADD	Benign	6.4
DANN	Benign	0.86

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: rs7512095; hg19: chr1-165721223;