19-17555744-C-A

Variant names:

• chr19-17555744-C-A
• rs898945714
• NM_024656.4:c.31C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024656.4(COLGALT1):​c.31C>A​(p.Arg11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 1,208,960 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. 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 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: COLGALT1 NM_024656.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.551
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14288643).

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>A	p.Arg11Ser	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.31C>A	p.Arg11Ser	missense	Exon 1 of 12	ENSP00000252599.3	Q8NBJ5
	COLGALT1	ENST00000886053.1		c.31C>A	p.Arg11Ser	missense	Exon 1 of 13	ENSP00000556112.1
	COLGALT1	ENST00000886054.1		c.31C>A	p.Arg11Ser	missense	Exon 1 of 14	ENSP00000556113.1

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151210 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000284 AC: 3 AN: 1057750 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 499714

African (AFR) AF: 0.0000915 AC: 2 AN: 21868

American (AMR) AF: 0.00 AC: 0 AN: 7548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13126

East Asian (EAS) AF: 0.00 AC: 0 AN: 24294

South Asian (SAS) AF: 0.00 AC: 0 AN: 19348

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2782

European-Non Finnish (NFE) AF: 0.00000110 AC: 1 AN: 906396

Other (OTH) AF: 0.00 AC: 0 AN: 41810

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151210 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 73842

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000242 AC: 1 AN: 41304

American (AMR) AF: 0.00 AC: 0 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10220

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67758

Other (OTH) AF: 0.00 AC: 0 AN: 2076

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	11
DANN	Benign	0.76
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.45	T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.55
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.24
Sift	Benign	0.060	T
Sift4G	Uncertain	0.045	D
Polyphen		0.36	B
Vest4		0.23
MutPred		0.15		Gain of glycosylation at R11 (P = 0.012)
MVP		0.29
MPC		0.32
ClinPred		0.22	T
GERP RS		2.6
PromoterAI		-0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.16
gMVP		0.63
Mutation Taster		=76/24	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: rs898945714; hg19: chr19-17666553;