16-70398428-G-C

Variant names:

• chr16-70398428-G-C
• rs774074693
• NM_006927.4:c.103C>G

Variant summary

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

The NM_006927.4(ST3GAL2):​c.103C>G​(p.Pro35Ala) 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 1,461,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ST3GAL2 NM_006927.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92

Genes affected

ST3GAL2 (HGNC:10863): (ST3 beta-galactoside alpha-2,3-sialyltransferase 2) 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 but can be proteolytically processed to a soluble form. This protein, which is a member of glycosyltransferase family 29, can use the same acceptor substrates as does sialyltransferase 4A. [provided by RefSeq, Jul 2008]

ENSG00000260111 (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=0.10162029).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL2	NM_006927.4	c.103C>G	p.Pro35Ala	missense_variant	Exon 2 of 7	ENST00000342907.3	NP_008858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST3GAL2	ENST00000342907.3	c.103C>G	p.Pro35Ala	missense_variant	Exon 2 of 7	5	NM_006927.4	ENSP00000345477.2
ST3GAL2	ENST00000393640.8	c.103C>G	p.Pro35Ala	missense_variant	Exon 1 of 6	1		ENSP00000377257.4
ENSG00000260111	ENST00000566960.1	n.211-695G>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461358 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726970

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

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.103C>G (p.P35A) alteration is located in exon 2 (coding exon 1) of the ST3GAL2 gene. This alteration results from a C to G substitution at nucleotide position 103, causing the proline (P) at amino acid position 35 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.070
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.72	.;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.044
Sift	Benign	0.24	T;T
Sift4G	Benign	0.48	T;T
Polyphen		0.0	B;B
Vest4		0.22
MutPred		0.46		Gain of catalytic residue at P35 (P = 0.0704);Gain of catalytic residue at P35 (P = 0.0704);
MVP		0.043
MPC		0.14
ClinPred		0.10	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs774074693; hg19: chr16-70432331;