1-43894442-G-C

Variant names:

• chr1-43894442-G-C
• rs201287443
• NM_006279.5:c.362G>C

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.86

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 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	c.362G>C	p.Arg121Pro	missense_variant	Exon 6 of 12	ENST00000347631.8	NP_006270.1

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251490 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135922

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.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	27
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	D
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	D
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	T
MutationAssessor	Benign	1.2	L;.;.;.;.;.;.;.;.;.;L;.;.;L;.;.;.;.;L;.;.;L;.;L;.;L;.;.;.;.;.;.
PrimateAI	Uncertain	0.64	T
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	D
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

Other links and lift over

dbSNP: rs201287443; hg19: chr1-44360114;