12-4776938-C-T

Variant summary

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

The ENST00000542998.5(GALNT8):c.311+11392C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,136 control chromosomes in the GnomAD database, including 2,225 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 0.17 (2225 hom., cov: 32)
• Consequence: GALNT8 ENST00000542998.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT8	ENST00000542998.5	c.311+11392C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25311 AN: 152018 Hom.: 2228 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0247

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.166 AC: 25310 AN: 152136 Hom.: 2225 Cov.: 32 AF XY: 0.165 AC XY: 12239 AN XY: 74370

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.0249

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.188

Alfa AF: 0.170 Hom.: 1227

Bravo AF: 0.159

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.0
Dann	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10492058; hg19: chr12-4886104;