19-17555854-G-C

Variant names:

• chr19-17555854-G-C
• NM_024656.4:c.141G>C
• COLGALT1 p.Ser47Ser

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_024656.4(COLGALT1):​c.141G>C​(p.Ser47Ser) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S47S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COLGALT1 NM_024656.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-0.335 with no splicing effect.

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.141G>C	p.Ser47Ser	synonymous	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.141G>C	p.Ser47Ser	synonymous	Exon 1 of 12	ENSP00000252599.3	Q8NBJ5
	COLGALT1	ENST00000886053.1		c.141G>C	p.Ser47Ser	synonymous	Exon 1 of 13	ENSP00000556112.1
	COLGALT1	ENST00000886054.1		c.141G>C	p.Ser47Ser	synonymous	Exon 1 of 14	ENSP00000556113.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1207752 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 588858

African (AFR) AF: 0.00 AC: 0 AN: 24518

American (AMR) AF: 0.00 AC: 0 AN: 14676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19068

East Asian (EAS) AF: 0.00 AC: 0 AN: 26968

South Asian (SAS) AF: 0.00 AC: 0 AN: 56936

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3416

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 984086

Other (OTH) AF: 0.00 AC: 0 AN: 48724

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.92
PhyloP100		-0.34
PromoterAI		0.025	Neutral

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-17666663;