2-154301419-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_052917.4(GALNT13):​c.986G>A​(p.Cys329Tyr) 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. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

GALNT13
NM_052917.4 missense

Scores

14
4
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.89
Variant links:
Genes affected
GALNT13 (HGNC:23242): (polypeptide N-acetylgalactosaminyltransferase 13) The GALNT13 protein is a member of the UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAcT; EC 2.4.1.41) family, which initiate O-linked glycosylation of mucins (see MUC3A, MIM 158371) by the initial transfer of N-acetylgalactosamine (GalNAc) with an alpha-linkage to a serine or threonine residue.[supplied by OMIM, Apr 2004]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.985

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GALNT13NM_052917.4 linkuse as main transcriptc.986G>A p.Cys329Tyr missense_variant 9/13 ENST00000392825.8 NP_443149.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GALNT13ENST00000392825.8 linkuse as main transcriptc.986G>A p.Cys329Tyr missense_variant 9/132 NM_052917.4 ENSP00000376570 P1Q8IUC8-1
GALNT13ENST00000409237.5 linkuse as main transcriptc.986G>A p.Cys329Tyr missense_variant 7/121 ENSP00000387239 Q8IUC8-3
GALNT13ENST00000431076.5 linkuse as main transcriptc.*806G>A 3_prime_UTR_variant, NMD_transcript_variant 7/91 ENSP00000389447
GALNT13ENST00000487047.1 linkuse as main transcriptn.288G>A non_coding_transcript_exon_variant 3/65

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 03, 2024The c.986G>A (p.C329Y) alteration is located in exon 9 (coding exon 7) of the GALNT13 gene. This alteration results from a G to A substitution at nucleotide position 986, causing the cysteine (C) at amino acid position 329 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.38
D
BayesDel_noAF
Pathogenic
0.31
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.70
D;.
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
1.0
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Pathogenic
0.30
D
MetaRNN
Pathogenic
0.98
D;D
MetaSVM
Uncertain
0.74
D
MutationAssessor
Pathogenic
4.1
H;H
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Pathogenic
-10
D;D
REVEL
Pathogenic
0.78
Sift
Uncertain
0.0010
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.95
MutPred
0.93
Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP
0.64
MPC
1.5
ClinPred
1.0
D
GERP RS
5.2
Varity_R
0.92
gMVP
0.99

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-155157932; API