rs4762737

Positions:

• chr12-22200249-G-A
• chr12-22200249-G-C

Variant summary

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

The NM_003034.4(ST8SIA1):​c.*1303C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,028 control chromosomes in the GnomAD database, including 45,659 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 0.77 (45658 hom., cov: 31)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: ST8SIA1 NM_003034.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33

Genes affected

ST8SIA1 (HGNC:10869): (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1) Gangliosides are membrane-bound glycosphingolipids containing sialic acid. Ganglioside GD3 is known to be important for cell adhesion and growth of cultured malignant cells. The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to GM3 to produce gangliosides GD3 and GT3. The encoded protein may be found in the Golgi apparatus and is a member of glycosyltransferase family 29. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2015]

ST8SIA1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST8SIA1	NM_003034.4	c.*1303C>T		3_prime_UTR_variant	5/5	ENST00000396037.9	NP_003025.1
ST8SIA1	NM_001304450.2	c.*1303C>T		3_prime_UTR_variant	4/4		NP_001291379.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST8SIA1	ENST00000396037.9	c.*1303C>T		3_prime_UTR_variant	5/5	1	NM_003034.4	ENSP00000379353.3
ST8SIA1	ENST00000544732.5	n.151+48757C>T		intron_variant		5
ST8SIA1	ENST00000545524.5	n.249+48757C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117461 AN: 151908 Hom.: 45617 Cov.: 31

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.813

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 1.00

GnomAD4 genome AF: 0.773 AC: 117557 AN: 152026 Hom.: 45658 Cov.: 31 AF XY: 0.776 AC XY: 57711 AN XY: 74322

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.841

Gnomad4 ASJ AF: 0.888

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.931

Gnomad4 FIN AF: 0.707

Gnomad4 NFE AF: 0.770

Gnomad4 OTH AF: 0.816

Alfa AF: 0.773 Hom.: 5763

Bravo AF: 0.778

Asia WGS AF: 0.887 AC: 3086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.37

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: rs4762737; hg19: chr12-22353183;