12-4776938-C-T

Variant names:

• chr12-4776938-C-T
• rs10492058
• ENST00000542998.5:c.309+11392C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000542998.5(GALNT8):​c.309+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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000542998.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT8	ENST00000542998.5	TSL:3	c.309+11392C>T		intron	N/A	ENSP00000440383.1	H0YFU9

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

African (AFR) AF: 0.141 AC: 5864 AN: 41522

American (AMR) AF: 0.129 AC: 1967 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 609 AN: 3466

East Asian (EAS) AF: 0.0249 AC: 129 AN: 5180

South Asian (SAS) AF: 0.128 AC: 618 AN: 4818

European-Finnish (FIN) AF: 0.198 AC: 2098 AN: 10574

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13436 AN: 67984

Other (OTH) AF: 0.188 AC: 396 AN: 2110

Alfa AF: 0.180 Hom.: 4961

Bravo AF: 0.159

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.37
PhyloP100		-0.27

Splicing

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

Other links and lift over

dbSNP: rs10492058; hg19: chr12-4886104;