rs149000966

Variant names:

• chr1-43920904-C-G
• rs149000966
• NM_006279.5:c.1014C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-43920904-C-G
• chr1-43920904-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_006279.5(ST3GAL3):​c.1014C>G​(p.Thr338Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,613,696 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T338T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00066 (2 hom., cov: 32)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: ST3GAL3 NM_006279.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.871

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]

ENSG00000284989 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 1-43920904-C-G is Benign according to our data. Variant chr1-43920904-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 530630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000664 (101/152180) while in subpopulation AFR AF= 0.00234 (97/41484). AF 95% confidence interval is 0.00196. There are 2 homozygotes in gnomad4. There are 49 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL3	NM_006279.5	c.1014C>G	p.Thr338Thr	synonymous_variant	Exon 11 of 12	ENST00000347631.8	NP_006270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST3GAL3	ENST00000347631.8	c.1014C>G	p.Thr338Thr	synonymous_variant	Exon 11 of 12	5	NM_006279.5	ENSP00000317192.6
ENSG00000284989	ENST00000645057.1	n.*2336C>G		non_coding_transcript_exon_variant	Exon 25 of 26			ENSP00000494063.1
ENSG00000284989	ENST00000645057.1	n.*2336C>G		3_prime_UTR_variant	Exon 25 of 26			ENSP00000494063.1

Frequencies

GnomAD3 genomes AF: 0.000664 AC: 101 AN: 152062 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.000164 AC: 41 AN: 250188 Hom.: 0 AF XY: 0.000126 AC XY: 17 AN XY: 135246

Gnomad AFR exome AF: 0.00229

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.0000575 AC: 84 AN: 1461516 Hom.: 0 Cov.: 37 AF XY: 0.0000509 AC XY: 37 AN XY: 727012

Gnomad4 AFR exome AF: 0.00212

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.000116

GnomAD4 genome AF: 0.000664 AC: 101 AN: 152180 Hom.: 2 Cov.: 32 AF XY: 0.000659 AC XY: 49 AN XY: 74410

Gnomad4 AFR AF: 0.00234

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.0000559 Hom.: 0

Bravo AF: 0.000782

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inborn genetic diseases Benign:1

Aug 09, 2018

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Early infantile epileptic encephalopathy with suppression bursts Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.3
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.27		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs149000966; hg19: chr1-44386576;