9-98844143-C-G

Variant names:

• chr9-98844143-C-G
• rs35616709
• NM_024642.5:c.1392C>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_024642.5(GALNT12):​c.1392C>G​(p.Pro464Pro) 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:7
• Conservation: PhyloP100: -1.02
• Publications: 4 publications found

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]

GALNT12 Gene-Disease associations (from GenCC):

• colorectal cancer, susceptibility to, 1

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 220673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.02 with no splicing effect.
• BS2: High AC in GnomAd4 at 424 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024642.5. 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
	GALNT12	NM_024642.5	MANE Select	c.1392C>G	p.Pro464Pro	synonymous	Exon 8 of 10	NP_078918.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT12	ENST00000375011.4	TSL:1 MANE Select	c.1392C>G	p.Pro464Pro	synonymous	Exon 8 of 10	ENSP00000364150.3	Q8IXK2-1
	GALNT12	ENST00000969913.1		c.1512C>G	p.Pro504Pro	synonymous	Exon 9 of 11	ENSP00000639972.1
	GALNT12	ENST00000969912.1		c.1437C>G	p.Pro479Pro	synonymous	Exon 9 of 11	ENSP00000639971.1

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

GnomAD2 exomes AF: 0.00309 AC: 777 AN: 251418 AF XY: 0.00336

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 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

African (AFR) AF: 0.000777 AC: 26 AN: 33474

American (AMR) AF: 0.00322 AC: 144 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00579 AC: 499 AN: 86252

European-Finnish (FIN) AF: 0.000824 AC: 44 AN: 53420

Middle Eastern (MID) AF: 0.00693 AC: 40 AN: 5768

European-Non Finnish (NFE) AF: 0.00411 AC: 4570 AN: 1111794

Other (OTH) AF: 0.00353 AC: 213 AN: 60390

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

African (AFR) AF: 0.000747 AC: 31 AN: 41524

American (AMR) AF: 0.00235 AC: 36 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00581 AC: 28 AN: 4820

European-Finnish (FIN) AF: 0.000378 AC: 4 AN: 10592

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00450 AC: 306 AN: 68026

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00169 Hom.: 0

Bravo AF: 0.00272

EpiCase AF: 0.00349

EpiControl AF: 0.00439

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Colorectal cancer, susceptibility to, 1 (1)
-	-	1	GALNT12-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.5
DANN	Benign	0.54
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism

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: rs35616709; hg19: chr9-101606425;