NM_005668.6:c.504-12403A>G

Variant names:

• chr5-100868799-T-C
• rs2059198
• NM_005668.6:c.504-12403A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005668.6(ST8SIA4):​c.504-12403A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 152,056 control chromosomes in the GnomAD database, including 57,027 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.86 (57027 hom., cov: 32)
• Consequence: ST8SIA4 NM_005668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST8SIA4	NM_005668.6	c.504-12403A>G		intron_variant	Intron 3 of 4	ENST00000231461.10	NP_005659.1
ST8SIA4	XM_005272078.4	c.504-12403A>G		intron_variant	Intron 3 of 4		XP_005272135.1
ST8SIA4	XM_011543630.3	c.503+17544A>G		intron_variant	Intron 3 of 3		XP_011541932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST8SIA4	ENST00000231461.10	c.504-12403A>G		intron_variant	Intron 3 of 4	1	NM_005668.6	ENSP00000231461.4

Frequencies

GnomAD3 genomes AF: 0.863 AC: 131110 AN: 151938 Hom.: 56963 Cov.: 32

Gnomad AFR AF: 0.953

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.848

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.863 AC: 131227 AN: 152056 Hom.: 57027 Cov.: 32 AF XY: 0.860 AC XY: 63906 AN XY: 74300

African (AFR) AF: 0.953 AC: 39607 AN: 41546

American (AMR) AF: 0.848 AC: 12954 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2993 AN: 3470

East Asian (EAS) AF: 0.615 AC: 3182 AN: 5178

South Asian (SAS) AF: 0.778 AC: 3756 AN: 4826

European-Finnish (FIN) AF: 0.837 AC: 8850 AN: 10574

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.841 AC: 57107 AN: 67882

Other (OTH) AF: 0.847 AC: 1781 AN: 2102

Alfa AF: 0.845 Hom.: 31562

Bravo AF: 0.864

Asia WGS AF: 0.748 AC: 2595 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.56
DANN	Benign	0.38
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs2059198; hg19: chr5-100204503; COSMIC: COSV51516310;