Genetic Variant NM_006279.5:c.362G>C (chr1-43894442-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_006279.5(ST3GAL3):c.362G>C(p.Arg121Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R121Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ST3GAL3
NM_006279.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.86

Variant links:

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 links:

ENSG00000284989 (HGNC:):

ENSG00000284989 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL3	NM_006279.5 link	c.362G>C	p.Arg121Pro	missense_variant	Exon 6 of 12	ENST00000347631.8	NP_006270.1	Q11203-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ST3GAL3	ENST00000347631.8 link	c.362G>C	p.Arg121Pro	missense_variant	Exon 6 of 12	5	NM_006279.5	ENSP00000317192.6	Q11203-1
ENSG00000284989	ENST00000645057.1 link	n.*1684G>C		non_coding_transcript_exon_variant	Exon 20 of 26			ENSP00000494063.1	A0A2R8Y4U1
ENSG00000284989	ENST00000645057.1 link	n.*1684G>C		3_prime_UTR_variant	Exon 20 of 26			ENSP00000494063.1	A0A2R8Y4U1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251490

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

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

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.095

T;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.96

.;D;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;.;.;D;D

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.59

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.31

MutationAssessor

Benign

1.2

L;.;.;.;.;.;.;.;.;.;L;.;.;L;.;.;.;.;L;.;.;L;.;L;.;L;.;.;.;.;.;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.3

.;N;N;D;.;N;.;.;.;.;N;.;.;.;.;N;.;.;.;N;.;D;D;N;N;N;N;.;D;N;.;.

REVEL

Benign

0.23

Sift

Benign

0.19

.;T;T;D;.;T;.;.;.;.;T;.;.;.;.;T;.;.;.;T;.;D;D;T;T;T;T;.;D;T;.;.

Sift4G

Benign

0.22

.;T;T;T;T;T;.;.;.;.;T;.;.;.;.;T;.;.;.;T;.;T;T;T;T;T;T;.;T;T;.;.

Polyphen

0.70

P;P;P;.;P;P;.;.;.;.;P;P;P;P;.;P;.;.;P;.;.;D;D;P;D;.;D;P;.;P;.;.

Vest4

0.74, 0.65, 0.74, 0.69, 0.74, 0.68, 0.71, 0.73, 0.75, 0.68, 0.74, 0.74, 0.74

MutPred

0.57

Loss of MoRF binding (P = 0.0156);.;.;.;.;.;Loss of MoRF binding (P = 0.0156);.;.;.;Loss of MoRF binding (P = 0.0156);.;.;Loss of MoRF binding (P = 0.0156);Loss of MoRF binding (P = 0.0156);.;Loss of MoRF binding (P = 0.0156);Loss of MoRF binding (P = 0.0156);Loss of MoRF binding (P = 0.0156);.;.;Loss of MoRF binding (P = 0.0156);.;Loss of MoRF binding (P = 0.0156);.;Loss of MoRF binding (P = 0.0156);.;.;.;.;.;.;

MVP

0.85

MPC

1.7

ClinPred

0.93

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.66

gMVP

0.91

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over