chr2-154409051-T-A

Position:

• chr2-154409051-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_052917.4(GALNT13):​c.1364T>A​(p.Ile455Lys) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GALNT13 NM_052917.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.906

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT13	NM_052917.4	c.1364T>A	p.Ile455Lys	missense_variant	11/13	ENST00000392825.8	NP_443149.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNT13	ENST00000392825.8	c.1364T>A	p.Ile455Lys	missense_variant	11/13	2	NM_052917.4	ENSP00000376570	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

The c.1364T>A (p.I455K) alteration is located in exon 11 (coding exon 9) of the GALNT13 gene. This alteration results from a T to A substitution at nucleotide position 1364, causing the isoleucine (I) at amino acid position 455 to be replaced by a lysine (K). 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	0.90
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	26
DANN	Benign	0.96
DEOGEN2	Benign	0.38	T;.;.
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Uncertain	0.089	D
MetaRNN	Pathogenic	0.91	D;D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Pathogenic	3.4	M;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-4.2	D;D;D
REVEL	Uncertain	0.55
Sift	Uncertain	0.012	D;D;D
Sift4G	Uncertain	0.036	D;D;D
Polyphen		0.94	P;.;.
Vest4		0.73
MutPred		0.82		Gain of disorder (P = 0.0026);Gain of disorder (P = 0.0026);.;
MVP		0.46
MPC		1.6
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.53
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr2-155265563;