19-17555729-CGCGCGGGCCGGCG-CGCGCGGGCCGGCGGCGCGGGCCGGCG

Variant names:

• chr19-17555729-C-CGCGCGGGCCGGCG
• rs2076205946
• NM_024656.4:c.25_37dupCGGCGGCGCGGGC

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Strong

The NM_024656.4(COLGALT1):​c.25_37dupCGGCGGCGCGGGC​(p.Gln13ProfsTer88) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000955 in 1,047,148 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 9.5e-7 (0 hom.)
• Consequence: COLGALT1 NM_024656.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.50
• Publications: 0 publications found

Genes affected

COLGALT1 (HGNC:26182): (collagen beta(1-O)galactosyltransferase 1) The protein encoded by this gene is one of two enzymes that transfers galactose moieties to hydroxylysine residues of collagen and mannose binding lectin. This gene is constitutively expressed and encodes a soluble protein that localizes to the endoplasmic reticulum. [provided by RefSeq, Dec 2015]

NIBAN3 (HGNC:24130): (niban apoptosis regulator 3)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 6 pathogenic variants in the truncated region.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024656.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLGALT1	NM_024656.4	MANE Select	c.25_37dupCGGCGGCGCGGGC	p.Gln13ProfsTer88	frameshift	Exon 1 of 12	NP_078932.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLGALT1	ENST00000252599.9	TSL:1 MANE Select	c.25_37dupCGGCGGCGCGGGC	p.Gln13ProfsTer88	frameshift	Exon 1 of 12	ENSP00000252599.3	Q8NBJ5
	COLGALT1	ENST00000886053.1		c.25_37dupCGGCGGCGCGGGC	p.Gln13ProfsTer88	frameshift	Exon 1 of 13	ENSP00000556112.1
	COLGALT1	ENST00000886054.1		c.25_37dupCGGCGGCGCGGGC	p.Gln13ProfsTer88	frameshift	Exon 1 of 14	ENSP00000556113.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.55e-7 AC: 1 AN: 1047148 Hom.: 0 Cov.: 29 AF XY: 0.00000202 AC XY: 1 AN XY: 494386

African (AFR) AF: 0.00 AC: 0 AN: 21480

American (AMR) AF: 0.00 AC: 0 AN: 7242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12626

East Asian (EAS) AF: 0.00 AC: 0 AN: 23218

South Asian (SAS) AF: 0.00 AC: 0 AN: 19026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2732

European-Non Finnish (NFE) AF: 0.00000111 AC: 1 AN: 899682

Other (OTH) AF: 0.00 AC: 0 AN: 41068

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.5

Splicing

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

Other links and lift over

dbSNP: rs2076205946; hg19: chr19-17666538;