rs12137475

chr1-43821476-C-T

Variant summary

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

The NM_006279.5(ST3GAL3):c.209+6543C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0812 in 152,108 control chromosomes in the GnomAD database, including 699 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 0.081 (699 hom., cov: 31)
• Consequence: ST3GAL3 NM_006279.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354

Genes affected

ST3GAL3 (HGNC:10866): (ST3 beta-galactoside alpha-2,3-sialyltransferase 3) The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The encoded protein is normally found in the Golgi apparatus but can be proteolytically processed to a soluble form. This protein is a member of glycosyltransferase family 29. Mutations in this gene have been associated with a form of autosomal recessive nonsymdromic cognitive disability as well as infantile epileptic encephalopathy. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST3GAL3	NM_006279.5	c.209+6543C>T		intron_variant		ENST00000347631.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST3GAL3	ENST00000347631.8	c.209+6543C>T		intron_variant		5	NM_006279.5	A1

Frequencies

GnomAD3 genomes AF: 0.0813 AC: 12350 AN: 151990 Hom.: 699 Cov.: 31

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0763

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0360

Gnomad FIN AF: 0.0716

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0938

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

GnomAD4 genome AF: 0.0812 AC: 12346 AN: 152108 Hom.: 699 Cov.: 31 AF XY: 0.0767 AC XY: 5704 AN XY: 74352

Gnomad4 AFR AF: 0.0217

Gnomad4 AMR AF: 0.0761

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0360

Gnomad4 FIN AF: 0.0716

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.0928

Alfa AF: 0.0968 Hom.: 209

Bravo AF: 0.0787

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.72
Dann	Benign	0.63

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: rs12137475; hg19: chr1-44287148;