rs2286580

Positions:

• chr12-4760762-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017417.2(GALNT8):​c.1174-196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,996 control chromosomes in the GnomAD database, including 11,562 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (11562 hom., cov: 31)
• Consequence: GALNT8 NM_017417.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830

Genes affected

GALNT8 (HGNC:4130): (polypeptide N-acetylgalactosaminyltransferase 8) This gene encodes a member of the UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes. GalNAc-Ts initiate mucin-type O-linked glycosylation in the Golgi apparatus by catalyzing the transfer of GalNAc to serine and threonine residues on target proteins. They are characterized by an N-terminal transmembrane domain, a stem region, a lumenal catalytic domain containing a GT1 motif and Gal/GalNAc transferase motif, and a C-terminal ricin/lectin-like domain. GalNAc-Ts have different, but overlapping, substrate specificities and patterns of expression. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNT8	NM_017417.2	c.1174-196A>G		intron_variant		ENST00000252318.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT8	ENST00000252318.7	c.1174-196A>G		intron_variant		1	NM_017417.2	P1
GALNT8	ENST00000648865.1	n.26-196A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58590 AN: 151878 Hom.: 11554 Cov.: 31

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.352

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.386 AC: 58631 AN: 151996 Hom.: 11562 Cov.: 31 AF XY: 0.384 AC XY: 28548 AN XY: 74298

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.348

Alfa AF: 0.397 Hom.: 2005

Bravo AF: 0.388

Asia WGS AF: 0.288 AC: 1006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	11
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs2286580; hg19: chr12-4869928; COSMIC: COSV52901548; COSMIC: COSV52901548;