chr5-100895747-C-A

Position:

• chr5-100895747-C-A

Variant summary

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

The NM_005668.6(ST8SIA4):​c.152G>T​(p.Ser51Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: ST8SIA4 NM_005668.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.253

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=0.12744027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST8SIA4	NM_005668.6	c.152G>T	p.Ser51Ile	missense_variant	2/5	ENST00000231461.10
ST8SIA4	NM_175052.3	c.152G>T	p.Ser51Ile	missense_variant	2/3
ST8SIA4	XM_005272078.4	c.152G>T	p.Ser51Ile	missense_variant	2/5
ST8SIA4	XM_011543630.3	c.152G>T	p.Ser51Ile	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST8SIA4	ENST00000231461.10	c.152G>T	p.Ser51Ile	missense_variant	2/5	1	NM_005668.6	P1
ST8SIA4	ENST00000451528.2	c.152G>T	p.Ser51Ile	missense_variant	2/3	1
ST8SIA4	ENST00000523381.1	c.*160G>T		3_prime_UTR_variant, NMD_transcript_variant	3/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Mar 08, 2024

The c.152G>T (p.S51I) 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 152, causing the serine (S) at amino acid position 51 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	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;N
MutationTaster	Benign	0.91	D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.79	N;N
REVEL	Benign	0.091
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.039	D;D
Polyphen		0.037	B;.
Vest4		0.37
MutPred		0.40		Loss of disorder (P = 0.0034);Loss of disorder (P = 0.0034);
MVP		0.068
MPC		0.62
ClinPred		0.64	D
GERP RS		3.2
Varity_R		0.12
gMVP		0.70

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: chr5-100231451;