rs734555

Positions:

• chr12-22297748-G-A

Variant summary

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

The NM_003034.4(ST8SIA1):​c.237-10455C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0554 in 152,128 control chromosomes in the GnomAD database, including 398 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 0.055 (398 hom., cov: 32)
• Consequence: ST8SIA1 NM_003034.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.582

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST8SIA1	NM_003034.4	c.237-10455C>T		intron_variant		ENST00000396037.9
ST8SIA1	NM_001304450.2	c.-83-10455C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST8SIA1	ENST00000396037.9	c.237-10455C>T		intron_variant		1	NM_003034.4	P1
ST8SIA1	ENST00000261197.7	c.237-10455C>T		intron_variant, NMD_transcript_variant		1
ST8SIA1	ENST00000540824.5	c.90-10455C>T		intron_variant		4
ST8SIA1	ENST00000541868.1	c.168-10455C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0556 AC: 8448 AN: 152010 Hom.: 402 Cov.: 32

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0476

Gnomad ASJ AF: 0.0456

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.0576

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0639

Gnomad OTH AF: 0.0570

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

GnomAD4 genome AF: 0.0554 AC: 8427 AN: 152128 Hom.: 398 Cov.: 32 AF XY: 0.0576 AC XY: 4281 AN XY: 74366

Gnomad4 AFR AF: 0.0125

Gnomad4 AMR AF: 0.0476

Gnomad4 ASJ AF: 0.0456

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0576

Gnomad4 NFE AF: 0.0639

Gnomad4 OTH AF: 0.0555

Alfa AF: 0.0602 Hom.: 55

Bravo AF: 0.0546

Asia WGS AF: 0.147 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.70

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: rs734555; hg19: chr12-22450682;