chr5-100895747-C-A

Variant names:

• chr5-100895747-C-A
• NM_005668.6:c.152G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12744027).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005668.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA4	NM_005668.6	MANE Select	c.152G>T	p.Ser51Ile	missense	Exon 2 of 5	NP_005659.1	Q92187-1
	ST8SIA4	NM_175052.3		c.152G>T	p.Ser51Ile	missense	Exon 2 of 3	NP_778222.1	Q92187-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA4	ENST00000231461.10	TSL:1 MANE Select	c.152G>T	p.Ser51Ile	missense	Exon 2 of 5	ENSP00000231461.4	Q92187-1
	ST8SIA4	ENST00000451528.2	TSL:1	c.152G>T	p.Ser51Ile	missense	Exon 2 of 3	ENSP00000428914.1	Q92187-2
	ST8SIA4	ENST00000881366.1		c.152G>T	p.Ser51Ile	missense	Exon 2 of 4	ENSP00000551425.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.25
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.091
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.039	D
Polyphen		0.037	B
Vest4		0.37
MutPred		0.40		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
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

hg19: chr5-100231451;