chr1-43930114-C-T

Variant names:

• chr1-43930114-C-T
• rs2108202
• NM_006279.5:c.1039-18C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_006279.5(ST3GAL3):​c.1039-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 1,612,870 control chromosomes in the GnomAD database, including 446,591 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (31732 hom., cov: 32)
  • Exomes 𝑓: 0.75 (414859 hom.)
• Consequence: ST3GAL3 NM_006279.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.239
• Publications: 24 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.025).
• BP6: Variant 1-43930114-C-T is Benign according to our data. Variant chr1-43930114-C-T is described in ClinVar as Benign. ClinVar VariationId is 262910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.777 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL3	NM_006279.5	MANE Select	c.1039-18C>T		intron	N/A	NP_006270.1
	ST3GAL3	NM_001350619.2		c.1280-18C>T		intron	N/A	NP_001337548.1
	ST3GAL3	NM_174963.5		c.1246-18C>T		intron	N/A	NP_777623.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL3	ENST00000347631.8	TSL:5 MANE Select	c.1039-18C>T		intron	N/A	ENSP00000317192.6
	ST3GAL3	ENST00000372372.7	TSL:1	c.1153-18C>T		intron	N/A	ENSP00000361447.2
	ST3GAL3	ENST00000361746.9	TSL:1	c.1132-18C>T		intron	N/A	ENSP00000354657.5

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91210 AN: 152006 Hom.: 31729 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.640

GnomAD2 exomes AF: 0.675 AC: 169443 AN: 250916 AF XY: 0.686

Gnomad AFR exome AF: 0.220

Gnomad AMR exome AF: 0.574

Gnomad ASJ exome AF: 0.682

Gnomad EAS exome AF: 0.641

Gnomad FIN exome AF: 0.754

Gnomad NFE exome AF: 0.777

Gnomad OTH exome AF: 0.696

GnomAD4 exome AF: 0.745 AC: 1088861 AN: 1460746 Hom.: 414859 Cov.: 35 AF XY: 0.744 AC XY: 540573 AN XY: 726778

African (AFR) AF: 0.204 AC: 6833 AN: 33448

American (AMR) AF: 0.582 AC: 26031 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 17885 AN: 26134

East Asian (EAS) AF: 0.566 AC: 22464 AN: 39690

South Asian (SAS) AF: 0.622 AC: 53626 AN: 86240

European-Finnish (FIN) AF: 0.758 AC: 40424 AN: 53298

Middle Eastern (MID) AF: 0.611 AC: 3520 AN: 5762

European-Non Finnish (NFE) AF: 0.788 AC: 875534 AN: 1111092

Other (OTH) AF: 0.705 AC: 42544 AN: 60360

GnomAD4 genome AF: 0.600 AC: 91236 AN: 152124 Hom.: 31732 Cov.: 32 AF XY: 0.598 AC XY: 44448 AN XY: 74374

African (AFR) AF: 0.232 AC: 9625 AN: 41496

American (AMR) AF: 0.630 AC: 9629 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2362 AN: 3472

East Asian (EAS) AF: 0.622 AC: 3209 AN: 5162

South Asian (SAS) AF: 0.611 AC: 2942 AN: 4818

European-Finnish (FIN) AF: 0.749 AC: 7931 AN: 10582

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.783 AC: 53236 AN: 67994

Other (OTH) AF: 0.639 AC: 1351 AN: 2114

Alfa AF: 0.709 Hom.: 63184

Bravo AF: 0.577

Asia WGS AF: 0.598 AC: 2080 AN: 3478

EpiCase AF: 0.777

EpiControl AF: 0.774

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Intellectual disability, autosomal recessive 12 Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Developmental and epileptic encephalopathy Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Developmental and epileptic encephalopathy, 15 Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.76
PhyloP100		0.24
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: rs2108202; hg19: chr1-44395786; COSMIC: COSV53521961; COSMIC: COSV53521961;