rs766750282
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_004482.4(GALNT3):c.803_804insC(p.Thr269AsnfsTer3) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
GALNT3
NM_004482.4 frameshift
NM_004482.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.87
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 Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 2-165761939-T-TG is Pathogenic according to our data. Variant chr2-165761939-T-TG is described in ClinVar as [Pathogenic]. Clinvar id is 7800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GALNT3 | NM_004482.4 | c.803_804insC | p.Thr269AsnfsTer3 | frameshift_variant | 4/11 | ENST00000392701.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GALNT3 | ENST00000392701.8 | c.803_804insC | p.Thr269AsnfsTer3 | frameshift_variant | 4/11 | 1 | NM_004482.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152176Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251352Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135840
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461862Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 727236
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Tumoral calcinosis, hyperphosphatemic, familial, 1 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 22, 2022 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2007 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | This sequence change creates a premature translational stop signal (p.Thr269Asnfs*3) in the GALNT3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GALNT3 are known to be pathogenic (PMID: 15133511, 20358599). This variant is present in population databases (rs766750282, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with clinical features of GALT1-related disorders (PMID: 17311862). ClinVar contains an entry for this variant (Variation ID: 7800). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
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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