chr1-165743318-G-GAAAA

Variant names:

• chr1-165743318-G-GAAAA
• NM_019026.6:c.324-11_324-8dupTTTT

Variant summary

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

The NM_019026.6(TMCO1):​c.324-11_324-8dupTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000016 in 1,252,528 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000016 (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.324-11_324-8dupTTTT		splice_region_variant, intron_variant	Intron 5 of 6	ENST00000367881.11	NP_061899.3
TMCO1	NM_001256164.1	c.375-11_375-8dupTTTT		splice_region_variant, intron_variant	Intron 5 of 6		NP_001243093.1
TMCO1	NM_001256165.1	c.288-11_288-8dupTTTT		splice_region_variant, intron_variant	Intron 5 of 6		NP_001243094.1
TMCO1	NR_045818.1	n.418-11_418-8dupTTTT		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.324-8_324-7insTTTT		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_019026.6	ENSP00000356856.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000160 AC: 2 AN: 1252528 Hom.: 0 Cov.: 0 AF XY: 0.00000319 AC XY: 2 AN XY: 627036

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000435

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000133

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-165712555;