Genetic Variant ST8SIA5:p.Gln272Pro (chr18-46680358-T-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_013305.6(ST8SIA5):c.815A>C(p.Gln272Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ST8SIA5
NM_013305.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.07

Variant links:

Genes affected

ST8SIA5 (HGNC:17827): (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 5) The protein encoded by this gene is a type II membrane protein that may be present in the Golgi apparatus. The encoded protein, which is a member of glycosyltransferase family 29, may be involved in the synthesis of gangliosides GD1c, GT1a, GQ1b, and GT3 from GD1a, GT1b, GM1b, and GD3, respectively. [provided by RefSeq, Jul 2008]

ST8SIA5 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
ST8SIA5	NM_013305.6 link	c.815A>C	p.Gln272Pro	missense_variant	Exon 7 of 7	ENST00000315087.12	NP_037437.2	O15466-1
ST8SIA5	NM_001307986.2 link	c.923A>C	p.Gln308Pro	missense_variant	Exon 8 of 8		NP_001294915.1	O15466-2
ST8SIA5	NM_001307987.2 link	c.722A>C	p.Gln241Pro	missense_variant	Exon 6 of 6		NP_001294916.1	O15466F5H8D1B7Z5F7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST8SIA5	ENST00000315087.12 link	c.815A>C	p.Gln272Pro	missense_variant	Exon 7 of 7	1	NM_013305.6	ENSP00000321343.6		O15466-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727236

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.815A>C (p.Q272P) alteration is located in exon 7 (coding exon 7) of the ST8SIA5 gene. This alteration results from a A to C substitution at nucleotide position 815, causing the glutamine (Q) at amino acid position 272 to be replaced by a proline (P). 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

0.22

BayesDel_addAF

Uncertain

0.056

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

.;T;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

T;T;T

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.63

D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

.;L;.

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.8

D;D;D

REVEL

Benign

0.19

Sift

Benign

0.055

T;D;D

Sift4G

Benign

0.091

T;T;T

Polyphen

0.96, 0.87

.;D;P

Vest4

0.57

MutPred

0.57

Gain of catalytic residue at P307 (P = 0.0164);.;.;

MVP

0.57

MPC

1.4

ClinPred

0.98

GERP RS

5.5

Varity_R

0.65

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.

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