rs3011225

Variant names:

• chr1-43853701-G-A
• rs3011225
• NM_006279.5:c.302+15390G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-43853701-G-A
• chr1-43853701-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006279.5(ST3GAL3):​c.302+15390G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 152,154 control chromosomes in the GnomAD database, including 31,455 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 0.60 (31455 hom., cov: 32)
• Consequence: ST3GAL3 NM_006279.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.971
• Publications: 25 publications found

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]

ST3GAL3 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 15

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• intellectual disability, autosomal recessive 12

  Inheritance: AR Classification: STRONG Submitted by: G2P
• complex neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000284989 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL3	NM_006279.5	c.302+15390G>A		intron_variant	Intron 5 of 11	ENST00000347631.8	NP_006270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST3GAL3	ENST00000347631.8	c.302+15390G>A		intron_variant	Intron 5 of 11	5	NM_006279.5	ENSP00000317192.6
ENSG00000284989	ENST00000645057.1	n.*1624+15390G>A		intron_variant	Intron 19 of 25			ENSP00000494063.1

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91445 AN: 152036 Hom.: 31451 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.641

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

GnomAD4 genome AF: 0.601 AC: 91472 AN: 152154 Hom.: 31455 Cov.: 32 AF XY: 0.599 AC XY: 44526 AN XY: 74388

African (AFR) AF: 0.259 AC: 10745 AN: 41518

American (AMR) AF: 0.558 AC: 8522 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2418 AN: 3470

East Asian (EAS) AF: 0.728 AC: 3757 AN: 5164

South Asian (SAS) AF: 0.559 AC: 2692 AN: 4816

European-Finnish (FIN) AF: 0.765 AC: 8109 AN: 10600

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52913 AN: 67990

Other (OTH) AF: 0.646 AC: 1365 AN: 2114

Alfa AF: 0.712 Hom.: 133025

Bravo AF: 0.574

Asia WGS AF: 0.638 AC: 2220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	13
DANN	Benign	0.43
PhyloP100		0.97
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3011225; hg19: chr1-44319373;