5-100886514-A-T

Variant names:

• chr5-100886514-A-T
• NM_005668.6:c.332T>A

Variant summary

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

The NM_005668.6(ST8SIA4):​c.332T>A​(p.Val111Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,668 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ST8SIA4 NM_005668.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.91

Genes affected

ST8SIA4 (HGNC:10871): (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 4) The protein encoded by this gene catalyzes the polycondensation of alpha-2,8-linked sialic acid required for the synthesis of polysialic acid, a modulator of the adhesive properties of neural cell adhesion molecule (NCAM1). The encoded protein, which is a member of glycosyltransferase family 29, is a type II membrane protein that may be present in the Golgi apparatus. Two transcript variants encoding different isoforms have been found for this gene. [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 rank	MANE	Protein	UniProt
ST8SIA4	NM_005668.6	c.332T>A	p.Val111Glu	missense_variant	Exon 3 of 5	ENST00000231461.10	NP_005659.1
ST8SIA4	NM_175052.3	c.332T>A	p.Val111Glu	missense_variant	Exon 3 of 3		NP_778222.1
ST8SIA4	XM_005272078.4	c.332T>A	p.Val111Glu	missense_variant	Exon 3 of 5		XP_005272135.1
ST8SIA4	XM_011543630.3	c.332T>A	p.Val111Glu	missense_variant	Exon 3 of 4		XP_011541932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST8SIA4	ENST00000231461.10	c.332T>A	p.Val111Glu	missense_variant	Exon 3 of 5	1	NM_005668.6	ENSP00000231461.4
ST8SIA4	ENST00000451528.2	c.332T>A	p.Val111Glu	missense_variant	Exon 3 of 3	1		ENSP00000428914.1
ST8SIA4	ENST00000507360.2	n.397T>A		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461668 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727134

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.332T>A (p.V111E) alteration is located in exon 3 (coding exon 3) of the ST8SIA4 gene. This alteration results from a T to A substitution at nucleotide position 332, causing the valine (V) at amino acid position 111 to be replaced by a glutamic acid (E). 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	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.067	T;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.48	N;N
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	1.6	N;N
REVEL	Uncertain	0.40
Sift	Benign	0.38	T;T
Sift4G	Benign	0.19	T;T
Polyphen		1.0	D;.
Vest4		0.82
MutPred		0.69		Gain of catalytic residue at V111 (P = 0.0059);Gain of catalytic residue at V111 (P = 0.0059);
MVP		0.33
MPC		1.8
ClinPred		0.80	D
GERP RS		5.9
Varity_R		0.35
gMVP		0.75

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: chr5-100222218;