dbSNP rs2076205946: COLGALT1:p.Arg9SerfsTer96 (chr19-17555729-CGCGCGGGCCGGCG-C) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_StrongPP5_Moderate

The NM_024656.4(COLGALT1):c.25_37delCGGCGGCGCGGGC(p.Arg9SerfsTer96) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000167 in 1,198,516 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 DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 9.5e-7 ( 0 hom. )

Consequence

COLGALT1
NM_024656.4 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 3.50

Publications

0 publications found

Variant links:

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]

COLGALT1 links:

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

NIBAN3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 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 7 pathogenic variants in the truncated region.

PP5

Variant 19-17555729-CGCGCGGGCCGGCG-C is Pathogenic according to our data. Variant chr19-17555729-CGCGCGGGCCGGCG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 2243995.Status of the report is criteria_provided_single_submitter, 1 stars.

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_37delCGGCGGCGCGGGC	p.Arg9SerfsTer96	frameshift	Exon 1 of 12	NP_078932.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COLGALT1	ENST00000252599.9	TSL:1 MANE Select	c.25_37delCGGCGGCGCGGGC	p.Arg9SerfsTer96	frameshift	Exon 1 of 12	ENSP00000252599.3	Q8NBJ5
COLGALT1	ENST00000886053.1		c.25_37delCGGCGGCGCGGGC	p.Arg9SerfsTer96	frameshift	Exon 1 of 13	ENSP00000556112.1
COLGALT1	ENST00000886054.1		c.25_37delCGGCGGCGCGGGC	p.Arg9SerfsTer96	frameshift	Exon 1 of 14	ENSP00000556113.1

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151364

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.55e-7

AC:

AN:

1047152

Hom.:

AF XY:

0.00

AC XY:

AN XY:

494388

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21480

American (AMR)

AF:

0.00

AC:

AN:

7242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12626

East Asian (EAS)

AF:

0.00

AC:

AN:

23218

South Asian (SAS)

AF:

0.00

AC:

AN:

19026

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20074

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2732

European-Non Finnish (NFE)

AF:

0.00000111

AC:

AN:

899686

Other (OTH)

AF:

0.00

AC:

AN:

41068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151364

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73902

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41332

American (AMR)

AF:

0.00

AC:

AN:

15184

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67790

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.5

Mutation Taster

=49/151

disease causing (fs/PTC)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over