5-100895765-C-A

Variant names:

• chr5-100895765-C-A
• rs368733661
• NM_005668.6:c.134G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005668.6(ST8SIA4):​c.134G>T​(p.Ser45Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• 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: 2.42

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21851104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST8SIA4	NM_005668.6	c.134G>T	p.Ser45Ile	missense_variant	Exon 2 of 5	ENST00000231461.10	NP_005659.1
ST8SIA4	NM_175052.3	c.134G>T	p.Ser45Ile	missense_variant	Exon 2 of 3		NP_778222.1
ST8SIA4	XM_005272078.4	c.134G>T	p.Ser45Ile	missense_variant	Exon 2 of 5		XP_005272135.1
ST8SIA4	XM_011543630.3	c.134G>T	p.Ser45Ile	missense_variant	Exon 2 of 4		XP_011541932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST8SIA4	ENST00000231461.10	c.134G>T	p.Ser45Ile	missense_variant	Exon 2 of 5	1	NM_005668.6	ENSP00000231461.4
ST8SIA4	ENST00000451528.2	c.134G>T	p.Ser45Ile	missense_variant	Exon 2 of 3	1		ENSP00000428914.1
ST8SIA4	ENST00000523381.1	n.*142G>T		non_coding_transcript_exon_variant	Exon 3 of 3	3		ENSP00000428826.1
ST8SIA4	ENST00000523381.1	n.*142G>T		3_prime_UTR_variant	Exon 3 of 3	3		ENSP00000428826.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460250 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726416

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.134G>T (p.S45I) alteration is located in exon 2 (coding exon 2) of the ST8SIA4 gene. This alteration results from a G to T substitution at nucleotide position 134, causing the serine (S) at amino acid position 45 to be replaced by an isoleucine (I). 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	0.15
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	-0.045
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;L
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.38	N;N
REVEL	Benign	0.087
Sift	Benign	0.18	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.040	B;.
Vest4		0.49
MVP		0.068
MPC		0.61
ClinPred		0.59	D
GERP RS		4.9
Varity_R		0.15
gMVP		0.84

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

LitVar

Other links and lift over

dbSNP: rs368733661; hg19: chr5-100231469;