rs201204481

chr1-43899643-C-Achr1-43899643-C-T

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_006279.5(ST3GAL3):c.660C>A(p.Tyr220Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. Y220Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ST3GAL3 NM_006279.5 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -1.69

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-43899643-C-A is Pathogenic according to our data. Variant chr1-43899643-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 995834.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST3GAL3	NM_006279.5	c.660C>A	p.Tyr220Ter	stop_gained	9/12	ENST00000347631.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST3GAL3	ENST00000347631.8	c.660C>A	p.Tyr220Ter	stop_gained	9/12	5	NM_006279.5	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Developmental and epileptic encephalopathy, 15 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.56	D
BayesDel_noAF	Pathogenic	0.57
Cadd	Pathogenic	31
Dann	Uncertain	0.99
Eigen	Benign	0.036
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.34	N
MutationTaster	Benign	1.0	A;A;A;A;A;A;A;A;A;A;A;A;A;A;A;D;D;D;D;D;D;D;D;D;D;D;D
Vest4		0.54, 0.56, 0.48, 0.54, 0.54
ClinPred		0.84	D
GERP RS		-3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs201204481; hg19: chr1-44365315;