12-22214139-G-A

Variant names:

• chr12-22214139-G-A
• rs722248
• NM_003034.4:c.585-12101C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003034.4(ST8SIA1):​c.585-12101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 151,940 control chromosomes in the GnomAD database, including 5,067 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 0.24 (5067 hom., cov: 32)
• Consequence: ST8SIA1 NM_003034.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003034.4. 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
	ST8SIA1	NM_003034.4	MANE Select	c.585-12101C>T		intron	N/A	NP_003025.1
	ST8SIA1	NM_001304450.2		c.156-12101C>T		intron	N/A	NP_001291379.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA1	ENST00000396037.9	TSL:1 MANE Select	c.585-12101C>T		intron	N/A	ENSP00000379353.3
	ST8SIA1	ENST00000261197.7	TSL:1	n.*67-12101C>T		intron	N/A	ENSP00000261197.3
	ST8SIA1	ENST00000540824.5	TSL:4	c.438-12101C>T		intron	N/A	ENSP00000441707.1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35802 AN: 151820 Hom.: 5048 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.236 AC: 35829 AN: 151940 Hom.: 5067 Cov.: 32 AF XY: 0.247 AC XY: 18330 AN XY: 74236

African (AFR) AF: 0.109 AC: 4523 AN: 41462

American (AMR) AF: 0.320 AC: 4883 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 776 AN: 3458

East Asian (EAS) AF: 0.483 AC: 2492 AN: 5160

South Asian (SAS) AF: 0.320 AC: 1537 AN: 4806

European-Finnish (FIN) AF: 0.365 AC: 3843 AN: 10534

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16878 AN: 67956

Other (OTH) AF: 0.233 AC: 488 AN: 2098

Alfa AF: 0.251 Hom.: 3242

Bravo AF: 0.226

Asia WGS AF: 0.387 AC: 1341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.9
DANN	Benign	0.42
PhyloP100		-0.10
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: rs722248; hg19: chr12-22367073;