rs80055718

Variant names:

• chr1-43920773-G-A
• rs80055718
• NM_006279.5:c.892-9G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006279.5(ST3GAL3):​c.892-9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 1,614,058 control chromosomes in the GnomAD database, including 3,083 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (211 hom., cov: 32)
  • Exomes 𝑓: 0.059 (2872 hom.)
• Consequence: ST3GAL3 NM_006279.5 intron
• Scores: Splicing: ADA: 0.0001221
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.45
• Publications: 3 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-43920773-G-A is Benign according to our data. Variant chr1-43920773-G-A is described in ClinVar as Benign. ClinVar VariationId is 130375.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006279.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL3	NM_006279.5	MANE Select	c.892-9G>A		intron	N/A	NP_006270.1	Q11203-1
	ST3GAL3	NM_001350619.2		c.937-9G>A		intron	N/A	NP_001337548.1	A0A2R8YDJ6
	ST3GAL3	NM_174963.5		c.1099-9G>A		intron	N/A	NP_777623.2	Q11203-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL3	ENST00000347631.8	TSL:5 MANE Select	c.892-9G>A		intron	N/A	ENSP00000317192.6	Q11203-1
	ST3GAL3	ENST00000372372.7	TSL:1	c.1006-9G>A		intron	N/A	ENSP00000361447.2	Q11203-19
	ST3GAL3	ENST00000361746.9	TSL:1	c.985-9G>A		intron	N/A	ENSP00000354657.5	A0A2U3TZK9

Frequencies

GnomAD3 genomes AF: 0.0434 AC: 6605 AN: 152090 Hom.: 209 Cov.: 32

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0323

Gnomad FIN AF: 0.0672

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.0320

GnomAD2 exomes AF: 0.0457 AC: 11465 AN: 251112 AF XY: 0.0466

Gnomad AFR exome AF: 0.0130

Gnomad AMR exome AF: 0.0336

Gnomad ASJ exome AF: 0.0287

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.0622

Gnomad NFE exome AF: 0.0632

Gnomad OTH exome AF: 0.0505

GnomAD4 exome AF: 0.0595 AC: 86915 AN: 1461850 Hom.: 2872 Cov.: 37 AF XY: 0.0588 AC XY: 42765 AN XY: 727228

African (AFR) AF: 0.0102 AC: 340 AN: 33480

American (AMR) AF: 0.0328 AC: 1469 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0283 AC: 739 AN: 26136

East Asian (EAS) AF: 0.000504 AC: 20 AN: 39700

South Asian (SAS) AF: 0.0350 AC: 3020 AN: 86256

European-Finnish (FIN) AF: 0.0626 AC: 3344 AN: 53414

Middle Eastern (MID) AF: 0.0192 AC: 111 AN: 5768

European-Non Finnish (NFE) AF: 0.0672 AC: 74679 AN: 1111980

Other (OTH) AF: 0.0529 AC: 3193 AN: 60392

GnomAD4 genome AF: 0.0435 AC: 6614 AN: 152208 Hom.: 211 Cov.: 32 AF XY: 0.0423 AC XY: 3150 AN XY: 74402

African (AFR) AF: 0.0125 AC: 519 AN: 41530

American (AMR) AF: 0.0313 AC: 479 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0254 AC: 88 AN: 3470

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5176

South Asian (SAS) AF: 0.0329 AC: 159 AN: 4826

European-Finnish (FIN) AF: 0.0672 AC: 712 AN: 10598

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0668 AC: 4542 AN: 67996

Other (OTH) AF: 0.0317 AC: 67 AN: 2114

Alfa AF: 0.0560 Hom.: 160

Bravo AF: 0.0388

Asia WGS AF: 0.0160 AC: 55 AN: 3478

EpiCase AF: 0.0574

EpiControl AF: 0.0573

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Developmental and epileptic encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.13
DANN	Benign	0.69
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		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: rs80055718; hg19: chr1-44386445; COSMIC: COSV53512497; COSMIC: COSV53512497;