9-98823259-C-T

Variant names:

• chr9-98823259-C-T
• rs114902755
• NM_024642.5:c.375C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_024642.5(GALNT12):​c.375C>T​(p.Cys125Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,614,040 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0059 (8 hom., cov: 33)
  • Exomes 𝑓: 0.00053 (5 hom.)
• Consequence: GALNT12 NM_024642.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.38
• Publications: 2 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 9-98823259-C-T is Benign according to our data. Variant chr9-98823259-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 241513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.38 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00589 (897/152256) while in subpopulation AFR AF = 0.0203 (841/41522). AF 95% confidence interval is 0.0191. There are 8 homozygotes in GnomAd4. There are 452 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 897 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.375C>T	p.Cys125Cys	synonymous	Exon 2 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.375C>T	p.Cys125Cys	synonymous	Exon 2 of 10	ENSP00000364150.3	Q8IXK2-1
	GALNT12	ENST00000969913.1		c.375C>T	p.Cys125Cys	synonymous	Exon 2 of 11	ENSP00000639972.1
	GALNT12	ENST00000969912.1		c.375C>T	p.Cys125Cys	synonymous	Exon 2 of 11	ENSP00000639971.1

Frequencies

GnomAD3 genomes AF: 0.00590 AC: 897 AN: 152138 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00158 AC: 397 AN: 251462 AF XY: 0.00127

Gnomad AFR exome AF: 0.0207

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000527

Gnomad OTH exome AF: 0.000977

GnomAD4 exome AF: 0.000534 AC: 780 AN: 1461784 Hom.: 5 Cov.: 32 AF XY: 0.000498 AC XY: 362 AN XY: 727206

African (AFR) AF: 0.0177 AC: 592 AN: 33476

American (AMR) AF: 0.00157 AC: 70 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1111920

Other (OTH) AF: 0.00144 AC: 87 AN: 60392

GnomAD4 genome AF: 0.00589 AC: 897 AN: 152256 Hom.: 8 Cov.: 33 AF XY: 0.00607 AC XY: 452 AN XY: 74448

African (AFR) AF: 0.0203 AC: 841 AN: 41522

American (AMR) AF: 0.00235 AC: 36 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68034

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00196 Hom.: 3

Bravo AF: 0.00646

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	12
DANN	Benign	0.70
PhyloP100		1.4
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs114902755; hg19: chr9-101585541;