rs12457104

Variant names:

• chr18-46753916-T-C
• rs12457104
• NM_013305.6:c.131+2462A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ST8SIA5	NM_013305.6	c.131+2462A>G		intron_variant	Intron 1 of 6	ENST00000315087.12	NP_037437.2
ST8SIA5	NM_001307986.2	c.131+2462A>G		intron_variant	Intron 1 of 7		NP_001294915.1
ST8SIA5	NM_001307987.2	c.131+2462A>G		intron_variant	Intron 1 of 5		NP_001294916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST8SIA5	ENST00000315087.12	c.131+2462A>G		intron_variant	Intron 1 of 6	1	NM_013305.6	ENSP00000321343.6

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

African (AFR) AF: 0.680 AC: 28152 AN: 41402

American (AMR) AF: 0.583 AC: 8913 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1516 AN: 3462

East Asian (EAS) AF: 0.690 AC: 3542 AN: 5130

South Asian (SAS) AF: 0.513 AC: 2465 AN: 4806

European-Finnish (FIN) AF: 0.504 AC: 5307 AN: 10524

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33777 AN: 67896

Other (OTH) AF: 0.561 AC: 1183 AN: 2110

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
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: rs12457104; hg19: chr18-44333879;