rs113954699

Variant names:

• chr1-43824851-C-T
• rs113954699
• ENST00000372372.7:c.282C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_174963.5(ST3GAL3):​c.375C>T​(p.Ser125Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000652 in 1,046,632 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00065 (2 hom.)
• Consequence: ST3GAL3 NM_174963.5 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -0.234

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]

ENSG00000284989 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-43824851-C-T is Benign according to our data. Variant chr1-43824851-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 212317.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
• BP7: Synonymous conserved (PhyloP=-0.234 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000657 (100/152260) while in subpopulation NFE AF= 0.00109 (74/68024). AF 95% confidence interval is 0.000888. There are 0 homozygotes in gnomad4. There are 44 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL3	NM_006279.5	c.209+9918C>T		intron_variant	Intron 4 of 11	ENST00000347631.8	NP_006270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST3GAL3	ENST00000347631.8	c.209+9918C>T		intron_variant	Intron 4 of 11	5	NM_006279.5	ENSP00000317192.6
ENSG00000284989	ENST00000645057.1	n.*1531+9918C>T		intron_variant	Intron 18 of 25			ENSP00000494063.1

Frequencies

GnomAD3 genomes AF: 0.000657 AC: 100 AN: 152142 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.000532 AC: 117 AN: 219784 Hom.: 0 AF XY: 0.000532 AC XY: 63 AN XY: 118478

Gnomad AFR exome AF: 0.000423

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000607

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000767

Gnomad OTH exome AF: 0.000712

GnomAD4 exome AF: 0.000651 AC: 582 AN: 894372 Hom.: 2 Cov.: 12 AF XY: 0.000641 AC XY: 299 AN XY: 466814

Gnomad4 AFR exome AF: 0.000355

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000543

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000190

Gnomad4 NFE exome AF: 0.000842

Gnomad4 OTH exome AF: 0.000432

GnomAD4 genome AF: 0.000657 AC: 100 AN: 152260 Hom.: 0 Cov.: 32 AF XY: 0.000591 AC XY: 44 AN XY: 74448

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00109

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.000834 Hom.: 0

Bravo AF: 0.000684

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Jul 22, 2015

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Dec 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ST3GAL3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.2
DANN	Benign	0.33

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: rs113954699; hg19: chr1-44290523; COSMIC: COSV99495218;