chr1-165743318-GA-G

Position:

• chr1-165743318-GA-G

Variant summary

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

The NM_019026.6(TMCO1):​c.324-8del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,155,014 control chromosomes in the GnomAD database, including 93 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.044 (66 hom., cov: 31)
  • Exomes 𝑓: 0.15 (27 hom.)
• Consequence: TMCO1 NM_019026.6 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:3
• 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-GA-G is Benign according to our data. Variant chr1-165743318-GA-G is described in ClinVar as [Benign]. Clinvar id is 767722.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-165743318-GA-G is described in Lovd as [Benign]. Variant chr1-165743318-GA-G is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMCO1	NM_019026.6	c.324-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000367881.11
TMCO1	NM_001256164.1	c.375-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
TMCO1	NM_001256165.1	c.288-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
TMCO1	NR_045818.1	n.418-8del		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.324-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_019026.6	P1

Frequencies

GnomAD3 genomes AF: 0.0435 AC: 4158 AN: 95506 Hom.: 65 Cov.: 31

Gnomad AFR AF: 0.0491

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0632

Gnomad ASJ AF: 0.00673

Gnomad EAS AF: 0.0662

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0454

Gnomad MID AF: 0.0441

Gnomad NFE AF: 0.0294

Gnomad OTH AF: 0.0404

GnomAD4 exome AF: 0.148 AC: 157240 AN: 1059494 Hom.: 27 Cov.: 0 AF XY: 0.149 AC XY: 78722 AN XY: 528270

Gnomad4 AFR exome AF: 0.160

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.148

Gnomad4 EAS exome AF: 0.203

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.0436 AC: 4167 AN: 95520 Hom.: 66 Cov.: 31 AF XY: 0.0483 AC XY: 2214 AN XY: 45792

Gnomad4 AFR AF: 0.0493

Gnomad4 AMR AF: 0.0640

Gnomad4 ASJ AF: 0.00673

Gnomad4 EAS AF: 0.0661

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0454

Gnomad4 NFE AF: 0.0295

Gnomad4 OTH AF: 0.0409

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 11, 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;