18-46680373-T-G

Position:

• chr18-46680373-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_013305.6(ST8SIA5):​c.800A>C​(p.Asp267Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ST8SIA5 NM_013305.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.764

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST8SIA5	NM_013305.6	c.800A>C	p.Asp267Ala	missense_variant	7/7	ENST00000315087.12	NP_037437.2
ST8SIA5	NM_001307986.2	c.908A>C	p.Asp303Ala	missense_variant	8/8		NP_001294915.1
ST8SIA5	NM_001307987.2	c.707A>C	p.Asp236Ala	missense_variant	6/6		NP_001294916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST8SIA5	ENST00000315087.12	c.800A>C	p.Asp267Ala	missense_variant	7/7	1	NM_013305.6	ENSP00000321343.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Nov 13, 2024

The c.800A>C (p.D267A) 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 800, causing the aspartic acid (D) at amino acid position 267 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	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	.;T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.76	D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.5	.;L;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.5	D;D;D
REVEL	Uncertain	0.46
Sift	Benign	0.048	D;D;D
Sift4G	Uncertain	0.047	D;T;D
Polyphen		1.0, 1.0	.;D;D
Vest4		0.76
MutPred		0.49		Loss of ubiquitination at K298 (P = 0.0924);.;.;
MVP		0.52
MPC		1.6
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.63
gMVP		0.88

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: chr18-44260336;