chr12-22248977-C-T

Variant names:

• chr12-22248977-C-T
• rs4762896
• NM_003034.4:c.584+29G>A

Variant summary

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

The NM_003034.4(ST8SIA1):​c.584+29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,527,574 control chromosomes in the GnomAD database, including 39,008 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 0.22 (3701 hom., cov: 32)
  • Exomes 𝑓: 0.22 (35307 hom.)
• Consequence: ST8SIA1 NM_003034.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 8 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.254 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.584+29G>A		intron	N/A	NP_003025.1
	ST8SIA1	NM_001304450.2		c.155+29G>A		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.584+29G>A		intron	N/A	ENSP00000379353.3
	ST8SIA1	ENST00000261197.7	TSL:1	n.*66+29G>A		intron	N/A	ENSP00000261197.3
	ST8SIA1	ENST00000541868.1	TSL:3	c.*25G>A		3_prime_UTR	Exon 4 of 4	ENSP00000440292.1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32700 AN: 151878 Hom.: 3696 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.0620

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.244

GnomAD2 exomes AF: 0.209 AC: 51345 AN: 246026 AF XY: 0.212

Gnomad AFR exome AF: 0.202

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.307

Gnomad EAS exome AF: 0.0517

Gnomad FIN exome AF: 0.134

Gnomad NFE exome AF: 0.236

Gnomad OTH exome AF: 0.237

GnomAD4 exome AF: 0.222 AC: 305235 AN: 1375572 Hom.: 35307 Cov.: 21 AF XY: 0.223 AC XY: 153626 AN XY: 688972

African (AFR) AF: 0.205 AC: 6467 AN: 31622

American (AMR) AF: 0.227 AC: 9939 AN: 43806

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 7774 AN: 25494

East Asian (EAS) AF: 0.0747 AC: 2929 AN: 39198

South Asian (SAS) AF: 0.201 AC: 16725 AN: 83056

European-Finnish (FIN) AF: 0.141 AC: 7484 AN: 53160

Middle Eastern (MID) AF: 0.318 AC: 1786 AN: 5612

European-Non Finnish (NFE) AF: 0.230 AC: 238768 AN: 1036140

Other (OTH) AF: 0.232 AC: 13363 AN: 57484

GnomAD4 genome AF: 0.215 AC: 32713 AN: 152002 Hom.: 3701 Cov.: 32 AF XY: 0.209 AC XY: 15528 AN XY: 74288

African (AFR) AF: 0.202 AC: 8365 AN: 41448

American (AMR) AF: 0.260 AC: 3974 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1044 AN: 3470

East Asian (EAS) AF: 0.0615 AC: 318 AN: 5168

South Asian (SAS) AF: 0.191 AC: 918 AN: 4812

European-Finnish (FIN) AF: 0.131 AC: 1385 AN: 10558

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.234 AC: 15916 AN: 67968

Other (OTH) AF: 0.247 AC: 522 AN: 2112

Alfa AF: 0.240 Hom.: 6147

Bravo AF: 0.225

Asia WGS AF: 0.155 AC: 540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.9
DANN	Benign	0.74
PhyloP100		-0.044
PromoterAI		-0.017	Neutral
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: rs4762896; hg19: chr12-22401911; COSMIC: COSV53954792;