rs397514537

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_001011551.3(C1GALT1C1):​c.577T>C​(p.Ser193Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 24)

Consequence

C1GALT1C1
NM_001011551.3 missense

Scores

4
10
3

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.24
Variant links:
Genes affected
C1GALT1C1 (HGNC:24338): (C1GALT1 specific chaperone 1) This gene encodes a type II transmembrane protein that is similar to the core 1 beta1,3-galactosyltransferase 1, which catalyzes the synthesis of the core-1 structure, also known as Thomsen-Friedenreich antigen, on O-linked glycans. This gene product lacks the galactosyltransferase activity itself, but instead acts as a molecular chaperone required for the folding, stability and full activity of the core 1 beta1,3-galactosyltransferase 1. Mutations in this gene have been associated with Tn syndrome. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Dec 2009]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.846
PP5
Variant X-120626590-A-G is Pathogenic according to our data. Variant chrX-120626590-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 39573.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-120626590-A-G is described in UniProt as null. Variant chrX-120626590-A-G is described in UniProt as null.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
C1GALT1C1NM_001011551.3 linkuse as main transcriptc.577T>C p.Ser193Pro missense_variant 2/2 ENST00000304661.6
C1GALT1C1NM_152692.5 linkuse as main transcriptc.577T>C p.Ser193Pro missense_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
C1GALT1C1ENST00000304661.6 linkuse as main transcriptc.577T>C p.Ser193Pro missense_variant 2/21 NM_001011551.3 P1
C1GALT1C1ENST00000371313.2 linkuse as main transcriptc.577T>C p.Ser193Pro missense_variant 3/31 P1

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
24

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Polyagglutinable erythrocyte syndrome Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMAug 01, 2008- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.030
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.67
D;D
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.81
.;T
M_CAP
Uncertain
0.15
D
MetaRNN
Pathogenic
0.85
D;D
MetaSVM
Benign
-0.62
T
MutationAssessor
Uncertain
2.8
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-3.1
D;D
REVEL
Uncertain
0.34
Sift
Uncertain
0.020
D;D
Sift4G
Uncertain
0.023
D;D
Polyphen
1.0
D;D
Vest4
0.67
MutPred
0.62
Loss of phosphorylation at S193 (P = 0.062);Loss of phosphorylation at S193 (P = 0.062);
MVP
0.70
MPC
1.0
ClinPred
0.98
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.87
gMVP
0.97

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs397514537; hg19: chrX-119760445; API