rs773763812

Variant names:

• chr1-43920880-C-G
• rs773763812
• NM_006279.5:c.990C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-43920880-C-G
• chr1-43920880-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006279.5(ST3GAL3):​c.990C>G​(p.Asn330Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N330S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ST3GAL3 NM_006279.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14817792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL3	NM_006279.5	c.990C>G	p.Asn330Lys	missense_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.990C>G	p.Asn330Lys	missense_variant	Exon 11 of 12	5	NM_006279.5	ENSP00000317192.6
ENSG00000284989	ENST00000645057.1	n.*2312C>G		non_coding_transcript_exon_variant	Exon 25 of 26			ENSP00000494063.1
ENSG00000284989	ENST00000645057.1	n.*2312C>G		3_prime_UTR_variant	Exon 25 of 26			ENSP00000494063.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461862 Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.0
DANN	Benign	0.91
DEOGEN2	Benign	0.11	T;.;.;.;.;.;.;.;T;.;.;.;.;T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.79	.;T;T;T;T;T;T;T;.;T;T;T;T;T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.15	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.30	N;.;.;.;.;.;.;.;N;.;.;.;.;N;.;.
PhyloP100		-2.6
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.7	.;N;N;N;.;.;.;.;.;.;N;.;.;.;.;N
REVEL	Benign	0.16
Sift	Benign	0.19	.;T;T;T;.;.;.;.;.;.;T;.;.;.;.;T
Sift4G	Benign	1.0	.;T;T;T;.;.;.;.;.;.;T;.;.;.;.;T
Polyphen		0.89	P;P;D;P;.;.;P;P;P;.;P;.;.;P;.;P
Vest4		0.47, 0.48, 0.47, 0.45, 0.51
MutPred		0.45		Gain of methylation at N330 (P = 0.0014);.;.;.;Gain of methylation at N330 (P = 0.0014);.;.;.;Gain of methylation at N330 (P = 0.0014);Gain of methylation at N330 (P = 0.0014);.;.;Gain of methylation at N330 (P = 0.0014);Gain of methylation at N330 (P = 0.0014);.;.;
MVP		0.24
MPC		1.4
ClinPred		0.84	D
GERP RS		-9.3
Varity_R		0.12
gMVP		0.24
Mutation Taster		=50/50

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: rs773763812; hg19: chr1-44386552;