chr2-154242107-C-G

Variant names:

• chr2-154242107-C-G
• rs1689521056
• NM_052917.4:c.389C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_052917.4(GALNT13):​c.389C>G​(p.Thr130Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T130I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: GALNT13 NM_052917.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.824

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052917.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT13	NM_052917.4	MANE Select	c.389C>G	p.Thr130Ser	missense	Exon 5 of 13	NP_443149.2	Q8IUC8-1
	GALNT13	NM_001376403.1		c.389C>G	p.Thr130Ser	missense	Exon 5 of 14	NP_001363332.1
	GALNT13	NM_001376404.1		c.389C>G	p.Thr130Ser	missense	Exon 5 of 14	NP_001363333.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT13	ENST00000392825.8	TSL:2 MANE Select	c.389C>G	p.Thr130Ser	missense	Exon 5 of 13	ENSP00000376570.3	Q8IUC8-1
	GALNT13	ENST00000409237.5	TSL:1	c.389C>G	p.Thr130Ser	missense	Exon 3 of 12	ENSP00000387239.1	Q8IUC8-3
	GALNT13	ENST00000431076.5	TSL:1	n.*209C>G		non_coding_transcript_exon	Exon 3 of 9	ENSP00000389447.1	H7BZG2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459646 Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2 AN XY: 726252

African (AFR) AF: 0.00 AC: 0 AN: 33412

American (AMR) AF: 0.00 AC: 0 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39570

South Asian (SAS) AF: 0.00 AC: 0 AN: 86110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110396

Other (OTH) AF: 0.00 AC: 0 AN: 60280

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.42	T
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.066	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	-0.057	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		7.9
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.057	T
Polyphen		1.0	D
Vest4		0.71
MutPred		0.76		Loss of catalytic residue at T130 (P = 0.1044)
MVP		0.38
MPC		1.1
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.57
gMVP		0.59
Mutation Taster		=33/67	disease causing

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

Other links and lift over

dbSNP: rs1689521056; hg19: chr2-155098620;