NM_006279.5:c.1038+15A>G

Variant names:

• chr1-43920943-A-G
• rs3120803
• NM_006279.5:c.1038+15A>G

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.1038+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 1,597,322 control chromosomes in the GnomAD database, including 652,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (55837 hom., cov: 30)
  • Exomes 𝑓: 0.91 (597033 hom.)
• Consequence: ST3GAL3 NM_006279.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.20
• Publications: 13 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: PanelApp Australia, 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=-0.94).
• BP6: Variant 1-43920943-A-G is Benign according to our data. Variant chr1-43920943-A-G is described in ClinVar as Benign. ClinVar VariationId is 262909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.92 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.1038+15A>G		intron	N/A	NP_006270.1	Q11203-1
	ST3GAL3	NM_001350619.2		c.1083+15A>G		intron	N/A	NP_001337548.1	A0A2R8YDJ6
	ST3GAL3	NM_174963.5		c.1245+15A>G		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.1038+15A>G		intron	N/A	ENSP00000317192.6	Q11203-1
	ST3GAL3	ENST00000372372.7	TSL:1	c.1152+15A>G		intron	N/A	ENSP00000361447.2	Q11203-19
	ST3GAL3	ENST00000361746.9	TSL:1	c.1131+15A>G		intron	N/A	ENSP00000354657.5	A0A2U3TZK9

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129294 AN: 151874 Hom.: 55812 Cov.: 30

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.928

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.874

GnomAD2 exomes AF: 0.881 AC: 197917 AN: 224564 AF XY: 0.886

Gnomad AFR exome AF: 0.695

Gnomad AMR exome AF: 0.848

Gnomad ASJ exome AF: 0.927

Gnomad EAS exome AF: 0.854

Gnomad FIN exome AF: 0.886

Gnomad NFE exome AF: 0.921

Gnomad OTH exome AF: 0.885

GnomAD4 exome AF: 0.908 AC: 1312307 AN: 1445328 Hom.: 597033 Cov.: 48 AF XY: 0.908 AC XY: 651461 AN XY: 717426

African (AFR) AF: 0.691 AC: 22868 AN: 33078

American (AMR) AF: 0.851 AC: 35549 AN: 41770

Ashkenazi Jewish (ASJ) AF: 0.926 AC: 23890 AN: 25788

East Asian (EAS) AF: 0.818 AC: 31824 AN: 38924

South Asian (SAS) AF: 0.868 AC: 73281 AN: 84388

European-Finnish (FIN) AF: 0.889 AC: 46417 AN: 52228

Middle Eastern (MID) AF: 0.864 AC: 4958 AN: 5736

European-Non Finnish (NFE) AF: 0.924 AC: 1020025 AN: 1103646

Other (OTH) AF: 0.895 AC: 53495 AN: 59770

GnomAD4 genome AF: 0.851 AC: 129369 AN: 151994 Hom.: 55837 Cov.: 30 AF XY: 0.850 AC XY: 63158 AN XY: 74296

African (AFR) AF: 0.699 AC: 28897 AN: 41356

American (AMR) AF: 0.876 AC: 13385 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.928 AC: 3221 AN: 3472

East Asian (EAS) AF: 0.849 AC: 4383 AN: 5164

South Asian (SAS) AF: 0.872 AC: 4196 AN: 4812

European-Finnish (FIN) AF: 0.882 AC: 9345 AN: 10600

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.926 AC: 62951 AN: 67992

Other (OTH) AF: 0.876 AC: 1848 AN: 2110

Alfa AF: 0.897 Hom.: 174924

Bravo AF: 0.843

Asia WGS AF: 0.853 AC: 2967 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Developmental and epileptic encephalopathy (1)
-	-	1	Developmental and epileptic encephalopathy, 15 (1)
-	-	1	Intellectual disability, autosomal recessive 12 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.13
DANN	Benign	0.57
PhyloP100		-1.2
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: rs3120803; hg19: chr1-44386615;