rs1265376699

Variant names:

• chr2-154242035-A-G
• rs1265376699
• NM_052917.4:c.317A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_052917.4(GALNT13):​c.317A>G​(p.Lys106Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,425,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GALNT13 NM_052917.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32
• Publications: 1 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2820928).

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.317A>G	p.Lys106Arg	missense	Exon 5 of 13	NP_443149.2	Q8IUC8-1
	GALNT13	NM_001376403.1		c.317A>G	p.Lys106Arg	missense	Exon 5 of 14	NP_001363332.1
	GALNT13	NM_001376404.1		c.317A>G	p.Lys106Arg	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.317A>G	p.Lys106Arg	missense	Exon 5 of 13	ENSP00000376570.3	Q8IUC8-1
	GALNT13	ENST00000409237.5	TSL:1	c.317A>G	p.Lys106Arg	missense	Exon 3 of 12	ENSP00000387239.1	Q8IUC8-3
	GALNT13	ENST00000431076.5	TSL:1	n.*137A>G		non_coding_transcript_exon	Exon 3 of 9	ENSP00000389447.1	H7BZG2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000447 AC: 1 AN: 223786 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000949

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1425246 Hom.: 0 Cov.: 28 AF XY: 0.00000141 AC XY: 1 AN XY: 708782

African (AFR) AF: 0.00 AC: 0 AN: 31536

American (AMR) AF: 0.00 AC: 0 AN: 36662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24412

East Asian (EAS) AF: 0.00 AC: 0 AN: 39068

South Asian (SAS) AF: 0.00 AC: 0 AN: 79634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52714

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5596

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1096910

Other (OTH) AF: 0.00 AC: 0 AN: 58714

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	0.0039	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.047
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.2	L
PhyloP100		9.3
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.23
Sift	Benign	0.28	T
Sift4G	Benign	0.45	T
Polyphen		0.0	B
Vest4		0.43
MutPred		0.40		Loss of methylation at K106 (P = 0.0174)
MVP		0.39
MPC		0.33
ClinPred		0.50	T
GERP RS		5.6
Varity_R		0.21
gMVP		0.56
Mutation Taster		=29/71	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1265376699; hg19: chr2-155098548;