chr2-154409041-A-G

Position:

• chr2-154409041-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052917.4(GALNT13):​c.1354A>G​(p.Lys452Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 9.32

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT13	NM_052917.4	c.1354A>G	p.Lys452Glu	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.1354A>G	p.Lys452Glu	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

Feb 05, 2024

The c.1354A>G (p.K452E) alteration is located in exon 11 (coding exon 9) of the GALNT13 gene. This alteration results from a A to G substitution at nucleotide position 1354, causing the lysine (K) at amino acid position 452 to be replaced by a glutamic acid (E). 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	0.73
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;.;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.4	N;N;D
REVEL	Uncertain	0.33
Sift	Benign	0.13	T;T;D
Sift4G	Benign	0.71	T;T;D
Polyphen		0.92	P;.;.
Vest4		0.79
MutPred		0.41		Loss of ubiquitination at K452 (P = 0.0107);Loss of ubiquitination at K452 (P = 0.0107);.;
MVP		0.42
MPC		0.82
ClinPred		0.92	D
GERP RS		5.3
Varity_R		0.43
gMVP		0.71

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: chr2-155265553;