1-43899577-C-A

Variant names:

• chr1-43899577-C-A
• NM_006279.5:c.594C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006279.5(ST3GAL3):​c.594C>A​(p.Asp198Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D198D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ST3GAL3 NM_006279.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.915

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL3	NM_006279.5	c.594C>A	p.Asp198Glu	missense_variant	Exon 9 of 12	ENST00000347631.8	NP_006270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST3GAL3	ENST00000347631.8	c.594C>A	p.Asp198Glu	missense_variant	Exon 9 of 12	5	NM_006279.5	ENSP00000317192.6
ENSG00000284989	ENST00000645057.1	n.*1916C>A		non_coding_transcript_exon_variant	Exon 23 of 26			ENSP00000494063.1
ENSG00000284989	ENST00000645057.1	n.*1916C>A		3_prime_UTR_variant	Exon 23 of 26			ENSP00000494063.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461640 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727118

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.52	D;.;.;.;.;.;.;.;.;.;.;D;.;.;.;.;D;.;.;.;.;.;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Pathogenic	0.99	.;D;D;D;D;D;D;D;D;D;D;.;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.92	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	-0.53	T
MutationAssessor	Pathogenic	3.2	M;.;.;.;.;.;.;.;M;.;.;M;.;.;.;.;M;.;.;M;.;.;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.6	.;D;N;D;.;.;.;.;D;.;.;.;.;D;.;.;.;D;.;D;.;D;.
REVEL	Uncertain	0.54
Sift	Uncertain	0.011	.;D;D;D;.;.;.;.;T;.;.;.;.;T;.;.;.;D;.;D;.;D;.
Sift4G	Uncertain	0.035	.;D;T;T;.;.;.;.;T;.;.;.;.;D;.;.;.;D;.;T;.;.;.
Polyphen		1.0	D;D;D;D;.;.;.;.;D;D;D;D;.;D;.;.;D;.;.;D;D;.;.
Vest4		0.91, 0.89, 0.89, 0.88, 0.91, 0.91, 0.89
MutPred		0.92		Gain of ubiquitination at K193 (P = 0.1008);.;.;.;Gain of ubiquitination at K193 (P = 0.1008);.;.;.;Gain of ubiquitination at K193 (P = 0.1008);.;.;Gain of ubiquitination at K193 (P = 0.1008);Gain of ubiquitination at K193 (P = 0.1008);.;.;Gain of ubiquitination at K193 (P = 0.1008);Gain of ubiquitination at K193 (P = 0.1008);.;.;Gain of ubiquitination at K193 (P = 0.1008);.;.;.;
MVP		0.83
MPC		1.4
ClinPred		0.97	D
GERP RS		-0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.70
gMVP		0.92

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-44365249;