19-17555827-C-G

Variant names:

• chr19-17555827-C-G
• rs7259723
• NM_024656.4:c.114C>G

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.114C>G​(p.Phe38Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F38F) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COLGALT1 NM_024656.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618
• Publications: 11 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]

COLGALT1 Gene-Disease associations (from GenCC):

• brain small vessel disease 3

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

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=0.1937941).

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.114C>G	p.Phe38Leu	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.114C>G	p.Phe38Leu	missense	Exon 1 of 12	ENSP00000252599.3	Q8NBJ5
	COLGALT1	ENST00000886053.1		c.114C>G	p.Phe38Leu	missense	Exon 1 of 13	ENSP00000556112.1
	COLGALT1	ENST00000886054.1		c.114C>G	p.Phe38Leu	missense	Exon 1 of 14	ENSP00000556113.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 2251

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Benign	-0.0032	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.75	T
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.74	N
PhyloP100		0.62
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.28
Sift	Benign	0.042	D
Sift4G	Uncertain	0.028	D
Polyphen		0.014	B
Vest4		0.27
MutPred		0.52		Loss of loop (P = 0.0512)
MVP		0.60
MPC		0.35
ClinPred		0.38	T
GERP RS		0.033
PromoterAI		-0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.64
Mutation Taster		=92/8	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: rs7259723; hg19: chr19-17666636;