chrX-120626227-C-G
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001011551.3(C1GALT1C1):c.940G>C(p.Gly314Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000058 in 1,207,154 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 24)
Exomes 𝑓: 0.0000037 ( 0 hom. 1 hem. )
Consequence
C1GALT1C1
NM_001011551.3 missense
NM_001011551.3 missense
Scores
1
5
10
Clinical Significance
Conservation
PhyloP100: 7.50
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 Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.17317975).
BS2
?
High Hemizygotes in GnomAdExome at 3 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C1GALT1C1 | NM_001011551.3 | c.940G>C | p.Gly314Arg | missense_variant | 2/2 | ENST00000304661.6 | |
C1GALT1C1 | NM_152692.5 | c.940G>C | p.Gly314Arg | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C1GALT1C1 | ENST00000304661.6 | c.940G>C | p.Gly314Arg | missense_variant | 2/2 | 1 | NM_001011551.3 | P1 | |
C1GALT1C1 | ENST00000371313.2 | c.940G>C | p.Gly314Arg | missense_variant | 3/3 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000265 AC: 3AN: 113074Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 35218
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GnomAD3 exomes AF: 0.0000223 AC: 4AN: 179618Hom.: 0 AF XY: 0.0000466 AC XY: 3AN XY: 64374
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GnomAD4 exome AF: 0.00000366 AC: 4AN: 1094080Hom.: 0 Cov.: 30 AF XY: 0.00000278 AC XY: 1AN XY: 359880
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 03, 2024 | The c.940G>C (p.G314R) alteration is located in exon 3 (coding exon 1) of the C1GALT1C1 gene. This alteration results from a G to C substitution at nucleotide position 940, causing the glycine (G) at amino acid position 314 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Polyagglutinable erythrocyte syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 849367). This variant has not been reported in the literature in individuals affected with C1GALT1C1-related conditions. This variant is present in population databases (rs749131756, gnomAD 0.03%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 314 of the C1GALT1C1 protein (p.Gly314Arg). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;P
Vest4
MutPred
Gain of catalytic residue at G314 (P = 0.0808);Gain of catalytic residue at G314 (P = 0.0808);
MVP
MPC
ClinPred
T
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at