9-98807694-G-A

Variant names:

• chr9-98807694-G-A
• NM_024642.5:c.-5G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024642.5(GALNT12):​c.-5G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GALNT12 NM_024642.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.85
• 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 Classification: LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000285706 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT12	NM_024642.5	c.-5G>A		5_prime_UTR_variant	Exon 1 of 10	ENST00000375011.4	NP_078918.3
LOC124902229	XR_007061689.1	n.-114C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT12	ENST00000375011.4	c.-5G>A		5_prime_UTR_variant	Exon 1 of 10	1	NM_024642.5	ENSP00000364150.3
ENSG00000285706	ENST00000647710.1	n.-130C>T		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 987700 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 470818

African (AFR) AF: 0.00 AC: 0 AN: 19156

American (AMR) AF: 0.00 AC: 0 AN: 5076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9740

East Asian (EAS) AF: 0.00 AC: 0 AN: 15050

South Asian (SAS) AF: 0.00 AC: 0 AN: 23732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2354

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 862918

Other (OTH) AF: 0.00 AC: 0 AN: 36058

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.-5G>A variant is located in the 5' untranslated region (5’ UTR) of the GALNT12 gene. This variant results from a G to A substitution 5 bases upstream from the first translated codon. This nucleotide position is well conserved in available vertebrate species. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.90
PhyloP100		1.9
PromoterAI		0.042	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr9-101569976;