rs267606841

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

Scores

12
5
2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.32
Variant links:
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]

Genome browser will be placed here

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
GALNT3NM_004482.4 linkuse as main transcriptc.1720T>G p.Cys574Gly missense_variant 10/11 ENST00000392701.8 NP_004473.2
GALNT3XM_005246449.2 linkuse as main transcriptc.1720T>G p.Cys574Gly missense_variant 10/11 XP_005246506.1
GALNT3XM_011510929.2 linkuse as main transcriptc.1720T>G p.Cys574Gly missense_variant 10/11 XP_011509231.1
GALNT3XM_017003770.2 linkuse as main transcriptc.1720T>G p.Cys574Gly missense_variant 10/11 XP_016859259.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GALNT3ENST00000392701.8 linkuse as main transcriptc.1720T>G p.Cys574Gly missense_variant 10/111 NM_004482.4 ENSP00000376465 P1Q14435-1
GALNT3ENST00000409882.5 linkuse as main transcriptc.934T>G p.Cys312Gly missense_variant 7/81 ENSP00000386955

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
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 providedliterature onlyOMIMApr 01, 2010- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.50
D
BayesDel_noAF
Pathogenic
0.48
CADD
Pathogenic
30
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.55
D;.
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.91
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.83
T;T
M_CAP
Pathogenic
0.56
D
MetaRNN
Pathogenic
0.99
D;D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Pathogenic
4.4
H;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.68
T
PROVEAN
Pathogenic
-7.3
D;D
REVEL
Pathogenic
0.95
Sift
Uncertain
0.010
D;D
Sift4G
Uncertain
0.011
D;D
Polyphen
1.0
D;.
Vest4
0.95
MutPred
0.89
Gain of loop (P = 0.002);.;
MVP
0.99
MPC
0.53
ClinPred
1.0
D
GERP RS
5.4
Varity_R
0.97
gMVP
0.95

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.24
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.24
Position offset: 0

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: rs267606841; hg19: chr2-166606311; API