rs17647532

Positions:

• chr18-35654108-T-C

Variant summary

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

The NM_020474.4(GALNT1):​c.-103-452T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,208 control chromosomes in the GnomAD database, including 1,066 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 0.11 (1066 hom., cov: 32)
• Consequence: GALNT1 NM_020474.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT1	NM_020474.4	c.-103-452T>C		intron_variant		ENST00000269195.6	NP_065207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNT1	ENST00000269195.6	c.-103-452T>C		intron_variant		1	NM_020474.4	ENSP00000269195	P1
GALNT1	ENST00000591924.5	c.-103-452T>C		intron_variant		3		ENSP00000465699
GALNT1	ENST00000589189.5	c.-103-452T>C		intron_variant, NMD_transcript_variant		5		ENSP00000465341
GALNT1	ENST00000586725.1	n.239-452T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17293 AN: 152090 Hom.: 1065 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0337

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.114 AC: 17305 AN: 152208 Hom.: 1066 Cov.: 32 AF XY: 0.115 AC XY: 8522 AN XY: 74424

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0336

Gnomad4 SAS AF: 0.0414

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.115

Alfa AF: 0.117 Hom.: 322

Bravo AF: 0.122

Asia WGS AF: 0.0550 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.5
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17647532; hg19: chr18-33234072;