rs12457104

Positions:

• chr18-46753916-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013305.6(ST8SIA5):​c.131+2462A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,816 control chromosomes in the GnomAD database, including 24,524 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 0.56 (24524 hom., cov: 31)
• Consequence: ST8SIA5 NM_013305.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278

Genes affected

ST8SIA5 (HGNC:17827): (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 5) The protein encoded by this gene is a type II membrane protein that may be present in the Golgi apparatus. The encoded protein, which is a member of glycosyltransferase family 29, may be involved in the synthesis of gangliosides GD1c, GT1a, GQ1b, and GT3 from GD1a, GT1b, GM1b, and GD3, respectively. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST8SIA5	NM_013305.6	c.131+2462A>G		intron_variant		ENST00000315087.12	NP_037437.2
ST8SIA5	NM_001307986.2	c.131+2462A>G		intron_variant			NP_001294915.1
ST8SIA5	NM_001307987.2	c.131+2462A>G		intron_variant			NP_001294916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST8SIA5	ENST00000315087.12	c.131+2462A>G		intron_variant		1	NM_013305.6	ENSP00000321343	P4

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85095 AN: 151696 Hom.: 24481 Cov.: 31

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.561 AC: 85196 AN: 151816 Hom.: 24524 Cov.: 31 AF XY: 0.562 AC XY: 41657 AN XY: 74170

Gnomad4 AFR AF: 0.680

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.561

Alfa AF: 0.549 Hom.: 3988

Bravo AF: 0.574

Asia WGS AF: 0.665 AC: 2312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.44

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: rs12457104; hg19: chr18-44333879;