rs201834329

Positions:

• chr1-43898237-A-G
• chr1-43898237-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006279.5(ST3GAL3):​c.400A>G​(p.Asn134Asp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000684 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. N134S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ST3GAL3 NM_006279.5 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.18

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20140567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST3GAL3	NM_006279.5	c.400A>G	p.Asn134Asp	missense_variant, splice_region_variant	7/12	ENST00000347631.8	NP_006270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST3GAL3	ENST00000347631.8	c.400A>G	p.Asn134Asp	missense_variant, splice_region_variant	7/12	5	NM_006279.5	ENSP00000317192.6
ENSG00000284989	ENST00000645057.1	n.*1722A>G		splice_region_variant, non_coding_transcript_exon_variant	21/26			ENSP00000494063.1
ENSG00000284989	ENST00000645057.1	n.*1722A>G		3_prime_UTR_variant	21/26			ENSP00000494063.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251260 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135830

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461626 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727122

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.069	T;.;.;.;.;.;.;.;.;.;.;.;T;.;.;.;.;T;.;.;.;.;.;.;.;.;.;.
Eigen	Benign	0.036
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	.;D;D;D;D;D;D;D;D;D;D;D;.;D;D;T;D;D;D;D;D;D;D;D;D;.;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.17	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N;.;.;.;.;.;.;.;.;N;.;.;N;.;.;.;.;N;.;.;N;.;N;.;.;.;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.74	.;N;N;.;N;.;.;.;.;N;.;.;.;.;N;.;.;.;N;.;N;N;N;N;.;N;.;.
REVEL	Benign	0.10
Sift	Benign	0.25	.;T;T;.;T;.;.;.;.;T;.;.;.;.;T;.;.;.;T;.;T;T;T;T;.;T;.;.
Sift4G	Benign	0.75	.;T;T;T;T;.;.;.;.;T;.;.;.;.;T;.;.;.;T;.;T;T;T;T;.;T;.;.
Polyphen		0.51	P;P;P;P;P;.;.;.;.;P;P;P;P;.;P;.;.;P;.;.;P;P;.;P;P;P;.;.
Vest4		0.48, 0.47, 0.42, 0.45, 0.46, 0.45, 0.48, 0.45, 0.47, 0.45, 0.49, 0.43
MutPred		0.45		Gain of ubiquitination at K137 (P = 0.0658);.;.;.;.;Gain of ubiquitination at K137 (P = 0.0658);.;.;.;Gain of ubiquitination at K137 (P = 0.0658);.;.;Gain of ubiquitination at K137 (P = 0.0658);Gain of ubiquitination at K137 (P = 0.0658);.;.;Gain of ubiquitination at K137 (P = 0.0658);Gain of ubiquitination at K137 (P = 0.0658);.;.;Gain of ubiquitination at K137 (P = 0.0658);.;Gain of ubiquitination at K137 (P = 0.0658);.;.;.;.;.;
MVP		0.20
MPC		1.2
ClinPred		0.64	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs201834329; hg19: chr1-44363909;