chr5-100863259-T-C

Variant names:

• chr5-100863259-T-C
• rs3776168
• NM_005668.6:c.504-6863A>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.504-6863A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,994 control chromosomes in the GnomAD database, including 11,809 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 0.39 (11809 hom., cov: 32)
• Consequence: ST8SIA4 NM_005668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA4	NM_005668.6	MANE Select	c.504-6863A>G		intron	N/A	NP_005659.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA4	ENST00000231461.10	TSL:1 MANE Select	c.504-6863A>G		intron	N/A	ENSP00000231461.4
	ST8SIA4	ENST00000956904.1		c.372-6863A>G		intron	N/A	ENSP00000626963.1
	ST8SIA4	ENST00000881366.1		c.246-6863A>G		intron	N/A	ENSP00000551425.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58649 AN: 151876 Hom.: 11773 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.386 AC: 58739 AN: 151994 Hom.: 11809 Cov.: 32 AF XY: 0.387 AC XY: 28785 AN XY: 74302

African (AFR) AF: 0.490 AC: 20297 AN: 41430

American (AMR) AF: 0.430 AC: 6563 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 932 AN: 3468

East Asian (EAS) AF: 0.292 AC: 1508 AN: 5170

South Asian (SAS) AF: 0.256 AC: 1234 AN: 4826

European-Finnish (FIN) AF: 0.355 AC: 3746 AN: 10554

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23342 AN: 67946

Other (OTH) AF: 0.365 AC: 772 AN: 2114

Alfa AF: 0.376 Hom.: 1696

Bravo AF: 0.396

Asia WGS AF: 0.289 AC: 1008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.37
PhyloP100		-0.17
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: rs3776168; hg19: chr5-100198963;