1-43930190-G-C

Variant names:

• chr1-43930190-G-C
• NM_006279.5:c.1097G>C

Variant summary

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

The NM_006279.5(ST3GAL3):​c.1097G>C​(p.Arg366Pro) 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 1,461,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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. R366H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ST3GAL3 NM_006279.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

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=0.2164205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL3	NM_006279.5	c.1097G>C	p.Arg366Pro	missense_variant	Exon 12 of 12	ENST00000347631.8	NP_006270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST3GAL3	ENST00000347631.8	c.1097G>C	p.Arg366Pro	missense_variant	Exon 12 of 12	5	NM_006279.5	ENSP00000317192.6
ENSG00000284989	ENST00000645057.1	n.*2419G>C		non_coding_transcript_exon_variant	Exon 26 of 26			ENSP00000494063.1
ENSG00000284989	ENST00000645057.1	n.*2419G>C		3_prime_UTR_variant	Exon 26 of 26			ENSP00000494063.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461668 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727148

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	0.0038	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;.;.;.;.;.;.;.;.;T;.;.;T;.;.;.;.;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.13	N
LIST_S2	Uncertain	0.90	.;D;D;D;D;D;D;D;D;.;D;D;D;D;D;D;D;D
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.22	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.63	T
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.0	.;N;N;N;.;.;N;.;.;.;N;.;.;.;N;.;.;.
REVEL	Benign	0.20
Sift	Benign	0.10	.;T;T;T;.;.;T;.;.;.;T;.;.;.;D;.;.;.
Sift4G	Uncertain	0.058	.;T;D;D;.;.;T;.;.;.;T;.;.;.;D;.;.;.
Polyphen		0.81	P;P;P;P;.;P;B;B;D;P;D;.;P;.;P;B;.;.
Vest4		0.65, 0.42, 0.42, 0.43, 0.40, 0.64
MutPred		0.63		Loss of MoRF binding (P = 2e-04);.;.;.;.;.;.;.;.;Loss of MoRF binding (P = 2e-04);.;.;Loss of MoRF binding (P = 2e-04);.;.;.;.;.;
MVP		0.84
MPC		1.6
ClinPred		0.97	D
GERP RS		-2.1
Varity_R		0.79

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: chr1-44395862;