1-165743038-A-G

Position:

• chr1-165743038-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_019026.6(TMCO1):​c.468+129T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0067 in 1,152,648 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0069 (35 hom.)
• Consequence: TMCO1 NM_019026.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0860

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-165743038-A-G is Benign according to our data. Variant chr1-165743038-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1191700.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMCO1	NM_019026.6	c.468+129T>C		intron_variant		ENST00000367881.11
TMCO1	NM_001256164.1	c.519+129T>C		intron_variant
TMCO1	NM_001256165.1	c.432+129T>C		intron_variant
TMCO1	NR_045818.1	n.562+129T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMCO1	ENST00000367881.11	c.468+129T>C		intron_variant		1	NM_019026.6	P1

Frequencies

GnomAD3 genomes AF: 0.00547 AC: 832 AN: 152218 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00546

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00970

Gnomad OTH AF: 0.00526

GnomAD4 exome AF: 0.00689 AC: 6888 AN: 1000312 Hom.: 35 AF XY: 0.00671 AC XY: 3428 AN XY: 510932

Gnomad4 AFR exome AF: 0.00130

Gnomad4 AMR exome AF: 0.00277

Gnomad4 ASJ exome AF: 0.00415

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000975

Gnomad4 FIN exome AF: 0.00594

Gnomad4 NFE exome AF: 0.00843

Gnomad4 OTH exome AF: 0.00512

GnomAD4 genome AF: 0.00546 AC: 831 AN: 152336 Hom.: 1 Cov.: 32 AF XY: 0.00486 AC XY: 362 AN XY: 74500

Gnomad4 AFR AF: 0.00130

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00546

Gnomad4 NFE AF: 0.00970

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00881 Hom.: 0

Bravo AF: 0.00470

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.83

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: rs149249499; hg19: chr1-165712275;