rs572958701

Variant names:

• chr1-43930190-G-A
• rs572958701
• NM_006279.5:c.1097G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-43930190-G-A
• chr1-43930190-G-C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_006279.5(ST3GAL3):​c.1097G>A​(p.Arg366His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,614,002 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R366R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000030 (1 hom.)
• Consequence: ST3GAL3 NM_006279.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 0.0400
• 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: 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.056435257).
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0000301 (44/1461668) while in subpopulation MID AF = 0.000356 (2/5622). AF 95% confidence interval is 0.000163. There are 1 homozygotes in GnomAdExome4. There are 29 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.1097G>A	p.Arg366His	missense	Exon 12 of 12	NP_006270.1	Q11203-1
	ST3GAL3	NM_174963.5		c.1304G>A	p.Arg435His	missense	Exon 13 of 13	NP_777623.2	Q11203-4
	ST3GAL3	NM_174968.5		c.1259G>A	p.Arg420His	missense	Exon 13 of 13	NP_777628.2	Q11203-13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL3	ENST00000347631.8	TSL:5 MANE Select	c.1097G>A	p.Arg366His	missense	Exon 12 of 12	ENSP00000317192.6	Q11203-1
	ST3GAL3	ENST00000372372.7	TSL:1	c.1211G>A	p.Arg404His	missense	Exon 12 of 12	ENSP00000361447.2	Q11203-19
	ST3GAL3	ENST00000361746.9	TSL:1	c.1190G>A	p.Arg397His	missense	Exon 13 of 13	ENSP00000354657.5	A0A2U3TZK9

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251422 AF XY: 0.0000294

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000301 AC: 44 AN: 1461668 Hom.: 1 Cov.: 32 AF XY: 0.0000399 AC XY: 29 AN XY: 727148

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000244 AC: 21 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.000356 AC: 2 AN: 5622

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1112010

Other (OTH) AF: 0.0000497 AC: 3 AN: 60370

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152334 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74480

African (AFR) AF: 0.00 AC: 0 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000313 Hom.: 0

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Developmental and epileptic encephalopathy (1)
-	1	-	Inborn genetic diseases (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	11
DANN	Benign	0.97
DEOGEN2	Benign	0.098	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.94	T
PhyloP100		0.040
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.021
Sift	Benign	0.15	T
Sift4G	Benign	0.069	T
Polyphen		0.0060	B
Vest4		0.23
MutPred		0.62		Loss of MoRF binding (P = 0.0024)
MVP		0.65
MPC		0.72
ClinPred		0.29	T
GERP RS		-2.1
Varity_R		0.020
Mutation Taster		=86/14	polymorphism

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: rs572958701; hg19: chr1-44395862;