Genetic Variant NM_006927.4:c.886G>C (chr16-70381856-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_006927.4(ST3GAL2):c.886G>C(p.Val296Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,260 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ST3GAL2
NM_006927.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.84

Variant links:

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]

ST3GAL2 links:

ENSG00000260111 (HGNC:):

ENSG00000260111 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
ST3GAL2	NM_006927.4 link	c.886G>C	p.Val296Leu	missense_variant	Exon 7 of 7	ENST00000342907.3	NP_008858.1	Q16842A0A024QZA4B3KXG9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ST3GAL2	ENST00000342907.3 link	c.886G>C	p.Val296Leu	missense_variant	Exon 7 of 7	5	NM_006927.4	ENSP00000345477.2	Q16842
ST3GAL2	ENST00000393640.8 link	c.886G>C	p.Val296Leu	missense_variant	Exon 6 of 6	1		ENSP00000377257.4	Q16842
ST3GAL2	ENST00000567822.1 link	n.407G>C		non_coding_transcript_exon_variant	Exon 5 of 5	3
ENSG00000260111	ENST00000566960.1 link	n.210+2190C>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461260

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726902

show subpopulations

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:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.886G>C (p.V296L) alteration is located in exon 7 (coding exon 6) of the ST3GAL2 gene. This alteration results from a G to C substitution at nucleotide position 886, causing the valine (V) at amino acid position 296 to be replaced by a leucine (L). 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

Pathogenic

0.57

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

0.073

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.75

.;T

M_CAP

Benign

0.038

MetaRNN

Uncertain

0.45

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.82

L;L

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.26

Sift

Benign

0.55

T;T

Sift4G

Benign

0.49

T;T

Polyphen

0.25

B;B

Vest4

0.61

MutPred

0.62

Loss of catalytic residue at V296 (P = 0.0376);Loss of catalytic residue at V296 (P = 0.0376);

MVP

0.38

MPC

0.88

ClinPred

0.90

GERP RS

6.1

Varity_R

0.34

gMVP

0.58

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over