19-17555733-C-T

Variant names:

• chr19-17555733-C-T
• rs1449330996
• NM_024656.4:c.20C>T

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.20C>T​(p.Ala7Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,200,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. A7G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: COLGALT1 NM_024656.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• 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]

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=0.093153626).

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.20C>T	p.Ala7Val	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.20C>T	p.Ala7Val	missense	Exon 1 of 12	ENSP00000252599.3	Q8NBJ5
	COLGALT1	ENST00000886053.1		c.20C>T	p.Ala7Val	missense	Exon 1 of 13	ENSP00000556112.1
	COLGALT1	ENST00000886054.1		c.20C>T	p.Ala7Val	missense	Exon 1 of 14	ENSP00000556113.1

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151256 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

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: 0.00000191 AC: 2 AN: 1049276 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 495402

African (AFR) AF: 0.00 AC: 0 AN: 21570

American (AMR) AF: 0.00 AC: 0 AN: 7298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12720

East Asian (EAS) AF: 0.00 AC: 0 AN: 23434

South Asian (SAS) AF: 0.00 AC: 0 AN: 19060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20210

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

European-Non Finnish (NFE) AF: 0.00000111 AC: 1 AN: 901042

Other (OTH) AF: 0.0000243 AC: 1 AN: 41206

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151364 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 73968

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15200

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

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10248

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67744

Other (OTH) AF: 0.00 AC: 0 AN: 2086

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.89
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.056
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.25
Sift	Benign	0.37	T
Sift4G	Benign	0.15	T
Polyphen		0.71	P
Vest4		0.16
MutPred		0.25		Loss of helix (P = 0.0376)
MVP		0.37
MPC		0.29
ClinPred		0.12	T
GERP RS		0.60
PromoterAI		-0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.029
gMVP		0.56
Mutation Taster		=86/14	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: rs1449330996; hg19: chr19-17666542;