rs267606841
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_004482.4(GALNT3):c.1720T>G(p.Cys574Gly) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 32)
Consequence
GALNT3
NM_004482.4 missense
NM_004482.4 missense
Scores
12
5
2
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
GALNT3 (HGNC:4125): (polypeptide N-acetylgalactosaminyltransferase 3) This gene encodes UDP-GalNAc transferase 3, a member of the GalNAc-transferases family. This family transfers an N-acetyl galactosamine to the hydroxyl group of a serine or threonine residue in the first step of O-linked oligosaccharide biosynthesis. Individual GalNAc-transferases have distinct activities and initiation of O-glycosylation is regulated by a repertoire of GalNAc-transferases. The protein encoded by this gene is highly homologous to other family members, however the enzymes have different substrate specificities. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.992
PP5
Variant 2-165749801-A-C is Pathogenic according to our data. Variant chr2-165749801-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 7803.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GALNT3 | NM_004482.4 | c.1720T>G | p.Cys574Gly | missense_variant | 10/11 | ENST00000392701.8 | NP_004473.2 | |
GALNT3 | XM_005246449.2 | c.1720T>G | p.Cys574Gly | missense_variant | 10/11 | XP_005246506.1 | ||
GALNT3 | XM_011510929.2 | c.1720T>G | p.Cys574Gly | missense_variant | 10/11 | XP_011509231.1 | ||
GALNT3 | XM_017003770.2 | c.1720T>G | p.Cys574Gly | missense_variant | 10/11 | XP_016859259.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GALNT3 | ENST00000392701.8 | c.1720T>G | p.Cys574Gly | missense_variant | 10/11 | 1 | NM_004482.4 | ENSP00000376465 | P1 | |
GALNT3 | ENST00000409882.5 | c.934T>G | p.Cys312Gly | missense_variant | 7/8 | 1 | ENSP00000386955 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Tumoral calcinosis, hyperphosphatemic, familial, 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2010 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Gain of loop (P = 0.002);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 0
Find out detailed SpliceAI scores and Pangolin per-transcript scores at