rs35632007

Positions:

• chr9-98846015-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_024642.5(GALNT12):​c.1497C>T​(p.Asn499=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,614,160 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (4 hom.)
• Consequence: GALNT12 NM_024642.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.788

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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 9-98846015-C-T is Benign according to our data. Variant chr9-98846015-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 221077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-98846015-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.788 with no splicing effect.
• BS2: High AC in GnomAd4 at 306 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNT12	NM_024642.5	c.1497C>T	p.Asn499=	synonymous_variant	9/10	ENST00000375011.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT12	ENST00000375011.4	c.1497C>T	p.Asn499=	synonymous_variant	9/10	1	NM_024642.5	P1

Frequencies

GnomAD3 genomes AF: 0.00201 AC: 306 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00329

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00181 AC: 456 AN: 251440 Hom.: 2 AF XY: 0.00192 AC XY: 261 AN XY: 135900

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000555

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00301

Gnomad OTH exome AF: 0.00407

GnomAD4 exome AF: 0.00269 AC: 3929 AN: 1461868 Hom.: 4 Cov.: 32 AF XY: 0.00267 AC XY: 1942 AN XY: 727236

Gnomad4 AFR exome AF: 0.000687

Gnomad4 AMR exome AF: 0.00130

Gnomad4 ASJ exome AF: 0.00203

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000464

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.00320

Gnomad4 OTH exome AF: 0.00250

GnomAD4 genome AF: 0.00201 AC: 306 AN: 152292 Hom.: 0 Cov.: 32 AF XY: 0.00209 AC XY: 156 AN XY: 74464

Gnomad4 AFR AF: 0.000602

Gnomad4 AMR AF: 0.00261

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00329

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00317 Hom.: 1

Bravo AF: 0.00228

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00316

EpiControl AF: 0.00403

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 17, 2021	- -

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Aug 10, 2016	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Nov 18, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	5.0
DANN	Benign	0.80

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

LitVar

Other links and lift over

dbSNP: rs35632007; hg19: chr9-101608297;