rs889395877

Variant names:

• chr9-98807723-C-G
• rs889395877
• NM_024642.5:c.25C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-98807723-C-G
• chr9-98807723-C-T
• chr9-98807723-C-A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP6 BS2

The NM_024642.5(GALNT12):​c.25C>G​(p.Arg9Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000687 in 1,179,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R9C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: GALNT12 NM_024642.5 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: 2.55
• Publications: 1 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

ENSG00000285706 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10485411).
• BP6: Variant 9-98807723-C-G is Benign according to our data. Variant chr9-98807723-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 410594.
• BS2: High AC in GnomAd4 at 57 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.25C>G	p.Arg9Gly	missense	Exon 1 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.25C>G	p.Arg9Gly	missense	Exon 1 of 10	ENSP00000364150.3	Q8IXK2-1
	GALNT12	ENST00000969913.1		c.25C>G	p.Arg9Gly	missense	Exon 1 of 11	ENSP00000639972.1
	GALNT12	ENST00000969912.1		c.25C>G	p.Arg9Gly	missense	Exon 1 of 11	ENSP00000639971.1

Frequencies

GnomAD3 genomes AF: 0.000380 AC: 57 AN: 150118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000233 AC: 24 AN: 1029610 Hom.: 0 Cov.: 30 AF XY: 0.0000242 AC XY: 12 AN XY: 496708

African (AFR) AF: 0.00121 AC: 24 AN: 19876

American (AMR) AF: 0.00 AC: 0 AN: 8266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11584

East Asian (EAS) AF: 0.00 AC: 0 AN: 15866

South Asian (SAS) AF: 0.00 AC: 0 AN: 32778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2512

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 884800

Other (OTH) AF: 0.00 AC: 0 AN: 37972

GnomAD4 genome AF: 0.000380 AC: 57 AN: 150118 Hom.: 0 Cov.: 32 AF XY: 0.000300 AC XY: 22 AN XY: 73252

African (AFR) AF: 0.00138 AC: 57 AN: 41200

American (AMR) AF: 0.00 AC: 0 AN: 15084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3434

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67294

Other (OTH) AF: 0.00 AC: 0 AN: 2066

Alfa AF: 0.000285 Hom.: 0

Bravo AF: 0.000434

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Benign	0.66
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.53	T
M_CAP	Pathogenic	0.51	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.6
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.081
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.056	T
Polyphen		0.078	B
Vest4		0.29
MutPred		0.29		Loss of methylation at R9 (P = 0.0442)
MVP		0.41
MPC		2.2
ClinPred		0.19	T
GERP RS		1.4
PromoterAI		-0.021	Neutral
Varity_R		0.12
gMVP		0.59
Mutation Taster		=95/5	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: rs889395877; hg19: chr9-101570005;