19-17555726-C-T

Variant names:

• chr19-17555726-C-T
• rs1012740258
• NM_024656.4:c.13C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BS1_Supporting

The NM_024656.4(COLGALT1):​c.13C>T​(p.Pro5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000326 in 1,197,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: COLGALT1 NM_024656.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.164
• Publications: 1 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: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07512128).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000132 (20/151500) while in subpopulation AFR AF = 0.000458 (19/41450). AF 95% confidence interval is 0.0003. There are 0 homozygotes in GnomAd4. There are 12 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.13C>T	p.Pro5Ser	missense	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.13C>T	p.Pro5Ser	missense	Exon 1 of 12	ENSP00000252599.3	Q8NBJ5
	COLGALT1	ENST00000886053.1		c.13C>T	p.Pro5Ser	missense	Exon 1 of 13	ENSP00000556112.1
	COLGALT1	ENST00000886054.1		c.13C>T	p.Pro5Ser	missense	Exon 1 of 14	ENSP00000556113.1

Frequencies

GnomAD3 genomes AF: 0.000132 AC: 20 AN: 151394 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000460

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000182 AC: 19 AN: 1045736 Hom.: 0 Cov.: 29 AF XY: 0.0000182 AC XY: 9 AN XY: 493684

African (AFR) AF: 0.000606 AC: 13 AN: 21440

American (AMR) AF: 0.00 AC: 0 AN: 7200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12574

East Asian (EAS) AF: 0.00 AC: 0 AN: 23106

South Asian (SAS) AF: 0.00 AC: 0 AN: 18970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19994

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2736

European-Non Finnish (NFE) AF: 0.00000445 AC: 4 AN: 898756

Other (OTH) AF: 0.0000488 AC: 2 AN: 40960

GnomAD4 genome AF: 0.000132 AC: 20 AN: 151500 Hom.: 0 Cov.: 31 AF XY: 0.000162 AC XY: 12 AN XY: 74034

African (AFR) AF: 0.000458 AC: 19 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67794

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000982

Asia WGS AF: 0.000291 AC: 1 AN: 3452

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.52	T
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.16
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.83	N
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.043	B
Vest4		0.13
MutPred		0.20		Gain of helix (P = 0.0034)
MVP		0.27
MPC		0.29
ClinPred		0.34	T
GERP RS		1.1
PromoterAI		0.17	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.18
gMVP		0.66
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs1012740258; hg19: chr19-17666535;