9-98807912-G-T

Variant names:

• chr9-98807912-G-T
• rs1439506011
• NM_024642.5:c.214G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_024642.5(GALNT12):​c.214G>T​(p.Ala72Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,212,172 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A72V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: GALNT12 NM_024642.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: -0.121
• 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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05083391).
• BS2: High AC in GnomAd4 at 8 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.214G>T	p.Ala72Ser	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.214G>T	p.Ala72Ser	missense	Exon 1 of 10	ENSP00000364150.3	Q8IXK2-1
	GALNT12	ENST00000969913.1		c.214G>T	p.Ala72Ser	missense	Exon 1 of 11	ENSP00000639972.1
	GALNT12	ENST00000969912.1		c.214G>T	p.Ala72Ser	missense	Exon 1 of 11	ENSP00000639971.1

Frequencies

GnomAD3 genomes AF: 0.0000534 AC: 8 AN: 149754 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.000119

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000127 AC: 135 AN: 1062418 Hom.: 0 Cov.: 30 AF XY: 0.000145 AC XY: 73 AN XY: 502848

African (AFR) AF: 0.00 AC: 0 AN: 22258

American (AMR) AF: 0.00 AC: 0 AN: 8162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13572

East Asian (EAS) AF: 0.00 AC: 0 AN: 24692

South Asian (SAS) AF: 0.00 AC: 0 AN: 21208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2828

European-Non Finnish (NFE) AF: 0.000147 AC: 133 AN: 907374

Other (OTH) AF: 0.0000476 AC: 2 AN: 41988

GnomAD4 genome AF: 0.0000534 AC: 8 AN: 149754 Hom.: 0 Cov.: 32 AF XY: 0.0000410 AC XY: 3 AN XY: 73108

African (AFR) AF: 0.00 AC: 0 AN: 41212

American (AMR) AF: 0.00 AC: 0 AN: 15026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000119 AC: 8 AN: 67326

Other (OTH) AF: 0.00 AC: 0 AN: 2058

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000340

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.81
DANN	Benign	0.74
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.042	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.12
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	0.59	N
REVEL	Benign	0.060
Sift	Benign	0.99	T
Sift4G	Benign	0.68	T
Polyphen		0.0	B
Vest4		0.049
MutPred		0.14		Gain of phosphorylation at A72 (P = 0.0354)
MVP		0.31
MPC		1.7
ClinPred		0.030	T
GERP RS		0.10
PromoterAI		-0.085	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.16
gMVP		0.50
Mutation Taster		=96/4	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: rs1439506011; hg19: chr9-101570194;