rs12963790

Positions:

• chr18-35693230-G-A

Variant summary

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

The NM_020474.4(GALNT1):​c.1299+910G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,084 control chromosomes in the GnomAD database, including 4,085 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 0.22 (4085 hom., cov: 32)
• Consequence: GALNT1 NM_020474.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.364

Genes affected

GALNT1 (HGNC:4123): (polypeptide N-acetylgalactosaminyltransferase 1) 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. Transcript variants derived from this gene that utilize alternative polyA signals have been described in the literature. [provided by RefSeq, Jul 2008]

LOC105372064 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT1	NM_020474.4	c.1299+910G>A		intron_variant		ENST00000269195.6	NP_065207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNT1	ENST00000269195.6	c.1299+910G>A		intron_variant		1	NM_020474.4	ENSP00000269195.4
GALNT1	ENST00000589189.5	n.*28+2005G>A		intron_variant		5		ENSP00000465341.1
GALNT1	ENST00000590654.1	n.*1219+910G>A		intron_variant		5		ENSP00000465452.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33565 AN: 151966 Hom.: 4079 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.221 AC: 33588 AN: 152084 Hom.: 4085 Cov.: 32 AF XY: 0.218 AC XY: 16233 AN XY: 74362

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.235

Alfa AF: 0.184 Hom.: 1533

Bravo AF: 0.240

Asia WGS AF: 0.133 AC: 460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.7
DANN	Benign	0.78

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: rs12963790; hg19: chr18-33273194;