Genetic Variant COLGALT1:p.Arg11Cys (chr19-17555744-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS1

The NM_024656.4(COLGALT1):c.31C>T(p.Arg11Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,208,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R11G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

COLGALT1
NM_024656.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.551

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11347073).

BS1

Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.00000851 (9/1057750) while in subpopulation AFR AF = 0.000183 (4/21868). AF 95% confidence interval is 0.0000615. There are 0 homozygotes in GnomAdExome4. There are 1 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. 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.31C>T	p.Arg11Cys	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.31C>T	p.Arg11Cys	missense	Exon 1 of 12	ENSP00000252599.3	Q8NBJ5
COLGALT1	ENST00000886053.1		c.31C>T	p.Arg11Cys	missense	Exon 1 of 13	ENSP00000556112.1
COLGALT1	ENST00000886054.1		c.31C>T	p.Arg11Cys	missense	Exon 1 of 14	ENSP00000556113.1

Frequencies

GnomAD3 genomes

AF:

0.0000331

AC:

AN:

151210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000851

AC:

AN:

1057750

Hom.:

Cov.:

AF XY:

0.00000200

AC XY:

AN XY:

499714

show subpopulations

African (AFR)

AF:

0.000183

AC:

AN:

21868

American (AMR)

AF:

0.00

AC:

AN:

7548

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13126

East Asian (EAS)

AF:

0.0000412

AC:

AN:

24294

South Asian (SAS)

AF:

0.00

AC:

AN:

19348

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2782

European-Non Finnish (NFE)

AF:

0.00000110

AC:

AN:

906396

Other (OTH)

AF:

0.0000718

AC:

AN:

41810

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

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:

0.0000331

AC:

AN:

151210

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73842

show subpopulations

African (AFR)

AF:

0.0000726

AC:

AN:

41304

American (AMR)

AF:

0.00

AC:

AN:

15164

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10220

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67758

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.555

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:

0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.019

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.58

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.69

PhyloP100

0.55

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.65

REVEL

Uncertain

0.30

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0060

Polyphen

0.0090

Vest4

0.14

MutPred

0.22

Loss of MoRF binding (P = 0.0092)

MVP

0.25

MPC

0.38

ClinPred

0.35

GERP RS

2.6

PromoterAI

-0.030

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.13

gMVP

0.58

Mutation Taster

=81/19

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