19-17555753-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_024656.4(COLGALT1):c.40C>T(p.Pro14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000568 in 1,214,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

COLGALT1
NM_024656.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.09

Publications

2 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: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.030822933).

BP6

Variant 19-17555753-C-T is Benign according to our data. Variant chr19-17555753-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1973108.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000337 (51/151376) while in subpopulation AFR AF = 0.00111 (46/41434). AF 95% confidence interval is 0.000855. There are 0 homozygotes in GnomAd4. There are 24 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

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.40C>T	p.Pro14Ser	missense	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.40C>T	p.Pro14Ser	missense	Exon 1 of 12	ENSP00000252599.3	Q8NBJ5
COLGALT1	ENST00000886053.1		c.40C>T	p.Pro14Ser	missense	Exon 1 of 13	ENSP00000556112.1
COLGALT1	ENST00000886054.1		c.40C>T	p.Pro14Ser	missense	Exon 1 of 14	ENSP00000556113.1

Frequencies

GnomAD3 genomes

AF:

0.000331

AC:

AN:

151268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000264

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:

0.0000169

AC:

AN:

1063540

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

502694

show subpopulations

African (AFR)

AF:

0.000407

AC:

AN:

22088

American (AMR)

AF:

0.000388

AC:

AN:

7736

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13418

East Asian (EAS)

AF:

0.00

AC:

AN:

24792

South Asian (SAS)

AF:

0.00

AC:

AN:

19570

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20752

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2814

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

910148

Other (OTH)

AF:

0.000142

AC:

AN:

42222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

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:

0.000337

AC:

AN:

151376

Hom.:

Cov.:

AF XY:

0.000324

AC XY:

AN XY:

73984

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

41434

American (AMR)

AF:

0.000264

AC:

AN:

15180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10232

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67772

Other (OTH)

AF:

0.00

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

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:

0.000285

Hom.:

Bravo

AF:

0.000389

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.6

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.016

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.33

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.031

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.69

PhyloP100

1.1

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.33

REVEL

Benign

0.11

Sift

Benign

1.0

Sift4G

Benign

0.67

Polyphen

0.0

Vest4

0.050

MutPred

0.22

Gain of helix (P = 0.0078)

MVP

0.095

MPC

0.29

ClinPred

0.11

GERP RS

1.1

PromoterAI

-0.019

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.018

gMVP

0.61

Mutation Taster

=92/8

polymorphism

(source)

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

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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