rs557604978

Variant names:

• chr9-98807836-G-A
• rs557604978
• NM_024642.5:c.138G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-98807836-G-A
• chr9-98807836-G-C
• chr9-98807836-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_024642.5(GALNT12):​c.138G>A​(p.Gly46Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 1,016,564 control chromosomes in the GnomAD database, including 7 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. G46G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0012 (6 hom., cov: 32)
  • Exomes 𝑓: 0.000066 (1 hom.)
• Consequence: GALNT12 NM_024642.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0180
• Publications: 0 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 9-98807836-G-A is Benign according to our data. Variant chr9-98807836-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 416213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.018 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.0000656 (57/869524) while in subpopulation AMR AF = 0.0211 (46/2178). AF 95% confidence interval is 0.0163. There are 1 homozygotes in GnomAdExome4. There are 25 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 178 AD,Unknown 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.138G>A	p.Gly46Gly	synonymous	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.138G>A	p.Gly46Gly	synonymous	Exon 1 of 10	ENSP00000364150.3	Q8IXK2-1
	GALNT12	ENST00000969913.1		c.138G>A	p.Gly46Gly	synonymous	Exon 1 of 11	ENSP00000639972.1
	GALNT12	ENST00000969912.1		c.138G>A	p.Gly46Gly	synonymous	Exon 1 of 11	ENSP00000639971.1

Frequencies

GnomAD3 genomes AF: 0.00118 AC: 174 AN: 146934 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000342

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

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: 0.0000909

Gnomad OTH AF: 0.00148

GnomAD2 exomes AF: 0.00 AC: 0 AN: 48 AF XY: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000656 AC: 57 AN: 869524 Hom.: 1 Cov.: 30 AF XY: 0.0000617 AC XY: 25 AN XY: 405338

African (AFR) AF: 0.000242 AC: 4 AN: 16500

American (AMR) AF: 0.0211 AC: 46 AN: 2178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6062

East Asian (EAS) AF: 0.00 AC: 0 AN: 5382

South Asian (SAS) AF: 0.00 AC: 0 AN: 17624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3866

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1780

European-Non Finnish (NFE) AF: 0.00000254 AC: 2 AN: 786734

Other (OTH) AF: 0.000170 AC: 5 AN: 29398

GnomAD4 genome AF: 0.00121 AC: 178 AN: 147040 Hom.: 6 Cov.: 32 AF XY: 0.00116 AC XY: 83 AN XY: 71602

African (AFR) AF: 0.000341 AC: 14 AN: 41052

American (AMR) AF: 0.0105 AC: 155 AN: 14792

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3390

East Asian (EAS) AF: 0.00 AC: 0 AN: 5096

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000909 AC: 6 AN: 65998

Other (OTH) AF: 0.00147 AC: 3 AN: 2044

Alfa AF: 0.00157 Hom.: 0

Bravo AF: 0.00251

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.5
DANN	Benign	0.89
PhyloP100		-0.018
PromoterAI		-0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs557604978; hg19: chr9-101570118;