2-154140349-G-A

Position:

• chr2-154140349-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052917.4(GALNT13):​c.155G>A​(p.Arg52Lys) 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 benign outcome for this variant. 14/21 in silico tools predict a benign 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: 8.04

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10126853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT13	NM_052917.4	c.155G>A	p.Arg52Lys	missense_variant	4/13	ENST00000392825.8	NP_443149.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNT13	ENST00000392825.8	c.155G>A	p.Arg52Lys	missense_variant	4/13	2	NM_052917.4	ENSP00000376570	P1
GALNT13	ENST00000409237.5	c.155G>A	p.Arg52Lys	missense_variant	2/12	1		ENSP00000387239
GALNT13	ENST00000431076.5	c.11G>A	p.Arg4Lys	missense_variant, NMD_transcript_variant	1/9	1		ENSP00000389447

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.155G>A (p.R52K) alteration is located in exon 4 (coding exon 2) of the GALNT13 gene. This alteration results from a G to A substitution at nucleotide position 155, causing the arginine (R) at amino acid position 52 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	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	23
DANN	Benign	0.86
DEOGEN2	Benign	0.049	T;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.18	N;N
MutationTaster	Benign	0.99	D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.33	N;N
REVEL	Benign	0.11
Sift	Benign	0.86	T;T
Sift4G	Benign	0.90	T;T
Polyphen		0.0	B;.
Vest4		0.32
MutPred		0.37		Gain of methylation at R52 (P = 0.0085);Gain of methylation at R52 (P = 0.0085);
MVP		0.13
MPC		0.40
ClinPred		0.23	T
GERP RS		5.3
Varity_R		0.083
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr2-154996862;