rs41306504

Variant names:

• chr9-98831821-G-A
• rs41306504
• NM_024642.5:c.781G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-98831821-G-A
• chr9-98831821-G-C
• chr9-98831821-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_024642.5(GALNT12):​c.781G>A​(p.Asp261Asn) variant causes a missense change. The variant allele was found at a frequency of 0.012 in 1,614,166 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D261H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.010 (12 hom., cov: 32)
  • Exomes 𝑓: 0.012 (152 hom.)
• Consequence: GALNT12 NM_024642.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 6.84
• Publications: 12 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 Classification: LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010009915).
• BP6: Variant 9-98831821-G-A is Benign according to our data. Variant chr9-98831821-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 241517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0122 (17892/1461884) while in subpopulation MID AF = 0.0194 (112/5768). AF 95% confidence interval is 0.0165. There are 152 homozygotes in GnomAdExome4. There are 9125 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1547 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.781G>A	p.Asp261Asn	missense	Exon 4 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.781G>A	p.Asp261Asn	missense	Exon 4 of 10	ENSP00000364150.3
	GALNT12	ENST00000969913.1		c.781G>A	p.Asp261Asn	missense	Exon 4 of 11	ENSP00000639972.1
	GALNT12	ENST00000969912.1		c.781G>A	p.Asp261Asn	missense	Exon 4 of 11	ENSP00000639971.1

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1546 AN: 152164 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00273

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.0250

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.0177

GnomAD2 exomes AF: 0.0119 AC: 2988 AN: 251464 AF XY: 0.0125

Gnomad AFR exome AF: 0.00234

Gnomad AMR exome AF: 0.00925

Gnomad ASJ exome AF: 0.00694

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0250

Gnomad NFE exome AF: 0.0130

Gnomad OTH exome AF: 0.0137

GnomAD4 exome AF: 0.0122 AC: 17892 AN: 1461884 Hom.: 152 Cov.: 32 AF XY: 0.0125 AC XY: 9125 AN XY: 727242

African (AFR) AF: 0.00227 AC: 76 AN: 33480

American (AMR) AF: 0.00953 AC: 426 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00704 AC: 184 AN: 26136

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39698

South Asian (SAS) AF: 0.0159 AC: 1373 AN: 86252

European-Finnish (FIN) AF: 0.0233 AC: 1247 AN: 53420

Middle Eastern (MID) AF: 0.0194 AC: 112 AN: 5768

European-Non Finnish (NFE) AF: 0.0123 AC: 13723 AN: 1112010

Other (OTH) AF: 0.0123 AC: 744 AN: 60396

GnomAD4 genome AF: 0.0102 AC: 1547 AN: 152282 Hom.: 12 Cov.: 32 AF XY: 0.0103 AC XY: 769 AN XY: 74464

African (AFR) AF: 0.00272 AC: 113 AN: 41554

American (AMR) AF: 0.0101 AC: 154 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.0145 AC: 70 AN: 4826

European-Finnish (FIN) AF: 0.0250 AC: 265 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0129 AC: 878 AN: 68018

Other (OTH) AF: 0.0175 AC: 37 AN: 2116

Alfa AF: 0.0108 Hom.: 37

Bravo AF: 0.00858

TwinsUK AF: 0.0113 AC: 42

ALSPAC AF: 0.0125 AC: 48

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.0114 AC: 98

ExAC AF: 0.0114 AC: 1385

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.0146

EpiControl AF: 0.0143

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	not specified (2)
-	-	1	Colorectal cancer, susceptibility to, 1 (1)
-	-	1	Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.44
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.2	L
PhyloP100		6.8
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.34
Sift	Benign	0.060	T
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.25
MPC		0.60
ClinPred		0.0091	T
GERP RS		5.7
Varity_R		0.70
gMVP		0.71
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs41306504; hg19: chr9-101594103; COSMIC: COSV66662367;