9-98844143-C-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_024642.5(GALNT12):c.1392C>G(p.Pro464=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00369 in 1,613,868 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P464P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0028 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (21 hom.)
• Consequence: GALNT12 NM_024642.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.02

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 9-98844143-C-G is Benign according to our data. Variant chr9-98844143-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 220673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-98844143-C-G is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-1.02 with no splicing effect.
• BS2: High AC in GnomAd at 424 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNT12	NM_024642.5	c.1392C>G	p.Pro464=	synonymous_variant	8/10	ENST00000375011.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT12	ENST00000375011.4	c.1392C>G	p.Pro464=	synonymous_variant	8/10	1	NM_024642.5	P1
GALNT12	ENST00000615204.1	n.254C>G		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.00279 AC: 424 AN: 152094 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.000749

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00450

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00309 AC: 777 AN: 251418 Hom.: 2 AF XY: 0.00336 AC XY: 456 AN XY: 135874

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00304

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00529

Gnomad FIN exome AF: 0.000554

Gnomad NFE exome AF: 0.00399

Gnomad OTH exome AF: 0.00473

GnomAD4 exome AF: 0.00379 AC: 5539 AN: 1461656 Hom.: 21 Cov.: 30 AF XY: 0.00396 AC XY: 2878 AN XY: 727154

Gnomad4 AFR exome AF: 0.000777

Gnomad4 AMR exome AF: 0.00322

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00579

Gnomad4 FIN exome AF: 0.000824

Gnomad4 NFE exome AF: 0.00411

Gnomad4 OTH exome AF: 0.00353

GnomAD4 genome AF: 0.00279 AC: 424 AN: 152212 Hom.: 5 Cov.: 33 AF XY: 0.00263 AC XY: 196 AN XY: 74430

Gnomad4 AFR AF: 0.000747

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00581

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.00450

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00242 Hom.: 0

Bravo AF: 0.00272

EpiCase AF: 0.00349

EpiControl AF: 0.00439

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	Aug 02, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Sep 09, 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. -

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 24, 2024	- -

GALNT12-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 11, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	1.5
Dann	Benign	0.54

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

LitVar

Other links and lift over

dbSNP: rs35616709; hg19: chr9-101606425;