chr1-165728260-CT-C

Variant names:

• chr1-165728260-CT-C
• rs397967679
• NM_019026.6:c.469-140delA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_019026.6(TMCO1):​c.469-140delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 407,164 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: TMCO1 NM_019026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355

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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMCO1	NM_019026.6	c.469-140delA		intron_variant	Intron 6 of 6	ENST00000367881.11	NP_061899.3
TMCO1	NM_001256164.1	c.520-140delA		intron_variant	Intron 6 of 6		NP_001243093.1
TMCO1	NM_001256165.1	c.433-140delA		intron_variant	Intron 6 of 6		NP_001243094.1
TMCO1	NR_045818.1	n.563-140delA		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMCO1	ENST00000367881.11	c.469-140delA		intron_variant	Intron 6 of 6	1	NM_019026.6	ENSP00000356856.6

Frequencies

GnomAD3 genomes AF: 0.00200 AC: 288 AN: 143920 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000734

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00342

Gnomad ASJ AF: 0.000596

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00936

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00189

Gnomad OTH AF: 0.00154

GnomAD4 exome AF: 0.172 AC: 45377 AN: 263194 Hom.: 0 AF XY: 0.173 AC XY: 25416 AN XY: 147004

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.197

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.00202 AC: 291 AN: 143970 Hom.: 0 Cov.: 31 AF XY: 0.00216 AC XY: 151 AN XY: 69848

Gnomad4 AFR AF: 0.000808

Gnomad4 AMR AF: 0.00341

Gnomad4 ASJ AF: 0.000596

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00936

Gnomad4 NFE AF: 0.00189

Gnomad4 OTH AF: 0.00152

ClinVar

Not reported in ClinVar

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: rs397967679; hg19: chr1-165697497;