rs1439506011

Variant names:

• chr9-98807912-G-A
• NM_024642.5:c.214G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-98807912-G-A
• chr9-98807912-G-T

Variant summary

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

The NM_024642.5(GALNT12):​c.214G>A​(p.Ala72Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GALNT12 NM_024642.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.121

Genes affected

GALNT12 (HGNC:19877): (polypeptide N-acetylgalactosaminyltransferase 12) This gene encodes a member of a family of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases, which catalyze the transfer of N-acetylgalactosamine (GalNAc) from UDP-GalNAc to a serine or threonine residue on a polypeptide acceptor in the initial step of O-linked protein glycosylation. Mutations in this gene are associated with an increased susceptibility to colorectal cancer.[provided by RefSeq, Mar 2011]

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=0.089588076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT12	NM_024642.5	c.214G>A	p.Ala72Thr	missense_variant	Exon 1 of 10	ENST00000375011.4	NP_078918.3
GALNT12	XM_006717287.1	c.-815G>A		upstream_gene_variant			XP_006717350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT12	ENST00000375011.4	c.214G>A	p.Ala72Thr	missense_variant	Exon 1 of 10	1	NM_024642.5	ENSP00000364150.3
GALNT12	ENST00000610463.1	n.-93G>A		upstream_gene_variant		4		ENSP00000477657.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1062418 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 502848

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.A72T variant (also known as c.214G>A), located in coding exon 1 of the GALNT12 gene, results from a G to A substitution at nucleotide position 214. The alanine at codon 72 is replaced by threonine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.1
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.11	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.0090
Sift	Benign	0.11	T
Sift4G	Benign	0.23	T
Polyphen		0.0080	B
Vest4		0.028
MutPred		0.20		Gain of glycosylation at A72 (P = 0.0111);
MVP		0.43
MPC		1.8
ClinPred		0.041	T
GERP RS		0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.098
gMVP		0.49

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: chr9-101570194;