1-165743318-GAAA-GA

Variant names:

• chr1-165743318-GAA-G
• rs751227407
• NM_019026.6:c.324-9_324-8delTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019026.6(TMCO1):​c.324-9_324-8delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,325,004 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000073 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (0 hom.)
• Consequence: TMCO1 NM_019026.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMCO1	NM_019026.6	c.324-9_324-8delTT		splice_region_variant, intron_variant	Intron 5 of 6	ENST00000367881.11	NP_061899.3
TMCO1	NM_001256164.1	c.375-9_375-8delTT		splice_region_variant, intron_variant	Intron 5 of 6		NP_001243093.1
TMCO1	NM_001256165.1	c.288-9_288-8delTT		splice_region_variant, intron_variant	Intron 5 of 6		NP_001243094.1
TMCO1	NR_045818.1	n.418-9_418-8delTT		splice_region_variant, intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMCO1	ENST00000367881.11	c.324-9_324-8delTT		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_019026.6	ENSP00000356856.6

Frequencies

GnomAD3 genomes AF: 0.0000836 AC: 8 AN: 95674 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000391

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00121

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000173

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000456

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00159 AC: 1959 AN: 1229314 Hom.: 0 AF XY: 0.00154 AC XY: 946 AN XY: 615772

Gnomad4 AFR exome AF: 0.00183

Gnomad4 AMR exome AF: 0.00360

Gnomad4 ASJ exome AF: 0.00200

Gnomad4 EAS exome AF: 0.00262

Gnomad4 SAS exome AF: 0.00191

Gnomad4 FIN exome AF: 0.00182

Gnomad4 NFE exome AF: 0.00140

Gnomad4 OTH exome AF: 0.00199

GnomAD4 genome AF: 0.0000732 AC: 7 AN: 95690 Hom.: 0 Cov.: 31 AF XY: 0.0000872 AC XY: 4 AN XY: 45892

Gnomad4 AFR AF: 0.0000390

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000909

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000173

Gnomad4 NFE AF: 0.0000456

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00259 Hom.: 1

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: rs751227407; hg19: chr1-165712555;