8-133463467-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_173344.3(ST3GAL1):c.684-8A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00784 in 1,613,740 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (9 hom., cov: 33)
  • Exomes 𝑓: 0.0080 (54 hom.)
• Consequence: ST3GAL1 NM_173344.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002539
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.792

Genes affected

ST3GAL1 (HGNC:10862): (ST3 beta-galactoside alpha-2,3-sialyltransferase 1) 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 but can be proteolytically processed to a soluble form. Correct glycosylation of the encoded protein may be critical to its sialyltransferase activity. This protein, which is a member of glycosyltransferase family 29, can use the same acceptor substrates as does sialyltransferase 4B. Two transcript variants encoding the same protein have been found for this gene. Other transcript variants may exist, but have not been fully characterized yet. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-133463467-T-C is Benign according to our data. Variant chr8-133463467-T-C is described in ClinVar as [Benign]. Clinvar id is 788872.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST3GAL1	NM_173344.3	c.684-8A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000522652.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST3GAL1	ENST00000522652.6	c.684-8A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_173344.3	P1
ST3GAL1	ENST00000521180.5	c.684-8A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		P1
ST3GAL1	ENST00000648219.1	c.684-8A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.00632 AC: 962 AN: 152116 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.00183

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00621

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00847

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00718 AC: 1794 AN: 249692 Hom.: 14 AF XY: 0.00732 AC XY: 987 AN XY: 134748

Gnomad AFR exome AF: 0.00168

Gnomad AMR exome AF: 0.00742

Gnomad ASJ exome AF: 0.0255

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00540

Gnomad FIN exome AF: 0.000694

Gnomad NFE exome AF: 0.00892

Gnomad OTH exome AF: 0.0119

GnomAD4 exome AF: 0.00800 AC: 11689 AN: 1461506 Hom.: 54 Cov.: 31 AF XY: 0.00799 AC XY: 5809 AN XY: 726998

Gnomad4 AFR exome AF: 0.00164

Gnomad4 AMR exome AF: 0.00743

Gnomad4 ASJ exome AF: 0.0224

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00526

Gnomad4 FIN exome AF: 0.000974

Gnomad4 NFE exome AF: 0.00862

Gnomad4 OTH exome AF: 0.00931

GnomAD4 genome AF: 0.00632 AC: 962 AN: 152234 Hom.: 9 Cov.: 33 AF XY: 0.00627 AC XY: 467 AN XY: 74428

Gnomad4 AFR AF: 0.00183

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.0233

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00622

Gnomad4 FIN AF: 0.000472

Gnomad4 NFE AF: 0.00847

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00875 Hom.: 9

Bravo AF: 0.00654

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.18
Dann	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0080
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: rs117461712; hg19: chr8-134475710;