18-46680358-T-G

Position:

• chr18-46680358-T-G

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ST8SIA5 NM_013305.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.07

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]

ACMG classification

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/exons	MANE	Protein	UniProt
ST8SIA5	NM_013305.6	c.815A>C	p.Gln272Pro	missense_variant	7/7	ENST00000315087.12	NP_037437.2
ST8SIA5	NM_001307986.2	c.923A>C	p.Gln308Pro	missense_variant	8/8		NP_001294915.1
ST8SIA5	NM_001307987.2	c.722A>C	p.Gln241Pro	missense_variant	6/6		NP_001294916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST8SIA5	ENST00000315087.12	c.815A>C	p.Gln272Pro	missense_variant	7/7	1	NM_013305.6	ENSP00000321343.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727236

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.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 21, 2024

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	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	.;T;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.63	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;L;.
PrimateAI	Uncertain	0.51	T
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	D
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.

Other links and lift over

hg19: chr18-44260321;