1-165743318-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_019026.6(TMCO1):c.324-8_324-7insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (0 hom., cov: 31)
  • Exomes 𝑓: 0.17 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMCO1 NM_019026.6 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.01

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.

• BP6: Variant 1-165743318-G-GA is Benign according to our data. Variant chr1-165743318-G-GA is described in ClinVar as [Benign]. Clinvar id is 770495.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMCO1	NM_019026.6	c.324-8_324-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000367881.11
TMCO1	NM_001256164.1	c.375-8_375-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
TMCO1	NM_001256165.1	c.288-8_288-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
TMCO1	NR_045818.1	n.418-8_418-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMCO1	ENST00000367881.11	c.324-8_324-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_019026.6	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 326 AN: 95570 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.00603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00146

Gnomad ASJ AF: 0.000898

Gnomad EAS AF: 0.00151

Gnomad SAS AF: 0.00703

Gnomad FIN AF: 0.00711

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00187

Gnomad OTH AF: 0.00388

GnomAD4 exome AF: 0.174 AC: 181488 AN: 1044954 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 87418 AN XY: 522108

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.0880

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.134

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.0954

Gnomad4 NFE exome AF: 0.189

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00345 AC: 330 AN: 95584 Hom.: 0 Cov.: 31 AF XY: 0.00402 AC XY: 184 AN XY: 45826

Gnomad4 AFR AF: 0.00613

Gnomad4 AMR AF: 0.00146

Gnomad4 ASJ AF: 0.000898

Gnomad4 EAS AF: 0.00152

Gnomad4 SAS AF: 0.00710

Gnomad4 FIN AF: 0.00711

Gnomad4 NFE AF: 0.00187

Gnomad4 OTH AF: 0.00463

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs751227407; hg19: chr1-165712555;