rs751227407

Variant names:

• chr1-165743318-GAAA-G
• rs751227407
• NM_019026.6:c.324-10_324-8delTTT

Your query was ambiguous. Multiple possible variants found:

• chr1-165743318-GAAA-G
• chr1-165743318-GAAA-GA
• chr1-165743318-GAAA-GAA
• chr1-165743318-GAAA-GAAAA
• chr1-165743318-GAAA-GAAAAA
• chr1-165743318-GAAA-GAAAAAA
• chr1-165743318-GAAA-GAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

Variant summary

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

The NM_019026.6(TMCO1):​c.324-10_324-8delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000684 in 1,345,488 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 0.000010 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000073 (0 hom.)
• Consequence: TMCO1 NM_019026.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.54

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.324-10_324-8delTTT		splice_region_variant, intron_variant	Intron 5 of 6	ENST00000367881.11	NP_061899.3
TMCO1	NM_001256164.1	c.375-10_375-8delTTT		splice_region_variant, intron_variant	Intron 5 of 6		NP_001243093.1
TMCO1	NM_001256165.1	c.288-10_288-8delTTT		splice_region_variant, intron_variant	Intron 5 of 6		NP_001243094.1
TMCO1	NR_045818.1	n.418-10_418-8delTTT		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.324-10_324-8delTTT		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_019026.6	ENSP00000356856.6

Frequencies

GnomAD3 genomes AF: 0.0000105 AC: 1 AN: 95686 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000173

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000728 AC: 91 AN: 1249802 Hom.: 0 AF XY: 0.0000527 AC XY: 33 AN XY: 625696

Gnomad4 AFR exome AF: 0.000108

Gnomad4 AMR exome AF: 0.000162

Gnomad4 ASJ exome AF: 0.0000436

Gnomad4 EAS exome AF: 0.0000279

Gnomad4 SAS exome AF: 0.0000399

Gnomad4 FIN exome AF: 0.000333

Gnomad4 NFE exome AF: 0.0000581

Gnomad4 OTH exome AF: 0.0000959

GnomAD4 genome AF: 0.0000105 AC: 1 AN: 95686 Hom.: 0 Cov.: 31 AF XY: 0.0000218 AC XY: 1 AN XY: 45864

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000173

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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;