12-22201987-A-G

Variant names:

• chr12-22201987-A-G
• rs704219
• NM_003034.4:c.636T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003034.4(ST8SIA1):​c.636T>C​(p.Ile212Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 1,613,074 control chromosomes in the GnomAD database, including 491,362 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 (45808 hom., cov: 31)
  • Exomes 𝑓: 0.78 (445554 hom.)
• Consequence: ST8SIA1 NM_003034.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.375
• Publications: 16 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=0.375 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST8SIA1	NM_003034.4	c.636T>C	p.Ile212Ile	synonymous_variant	Exon 5 of 5	ENST00000396037.9	NP_003025.1
ST8SIA1	NM_001304450.2	c.207T>C	p.Ile69Ile	synonymous_variant	Exon 4 of 4		NP_001291379.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST8SIA1	ENST00000396037.9	c.636T>C	p.Ile212Ile	synonymous_variant	Exon 5 of 5	1	NM_003034.4	ENSP00000379353.3

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117648 AN: 151902 Hom.: 45767 Cov.: 31

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.814

GnomAD2 exomes AF: 0.808 AC: 200388 AN: 247918 AF XY: 0.814

Gnomad AFR exome AF: 0.725

Gnomad AMR exome AF: 0.858

Gnomad ASJ exome AF: 0.880

Gnomad EAS exome AF: 0.844

Gnomad FIN exome AF: 0.716

Gnomad NFE exome AF: 0.776

Gnomad OTH exome AF: 0.814

GnomAD4 exome AF: 0.779 AC: 1138146 AN: 1461054 Hom.: 445554 Cov.: 45 AF XY: 0.784 AC XY: 570100 AN XY: 726816

African (AFR) AF: 0.723 AC: 24158 AN: 33434

American (AMR) AF: 0.857 AC: 38251 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 22982 AN: 26104

East Asian (EAS) AF: 0.861 AC: 34182 AN: 39692

South Asian (SAS) AF: 0.930 AC: 80138 AN: 86146

European-Finnish (FIN) AF: 0.722 AC: 38486 AN: 53322

Middle Eastern (MID) AF: 0.892 AC: 5138 AN: 5758

European-Non Finnish (NFE) AF: 0.762 AC: 846915 AN: 1111602

Other (OTH) AF: 0.793 AC: 47896 AN: 60368

GnomAD4 genome AF: 0.775 AC: 117744 AN: 152020 Hom.: 45808 Cov.: 31 AF XY: 0.778 AC XY: 57776 AN XY: 74308

African (AFR) AF: 0.730 AC: 30261 AN: 41452

American (AMR) AF: 0.843 AC: 12867 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3078 AN: 3470

East Asian (EAS) AF: 0.846 AC: 4366 AN: 5158

South Asian (SAS) AF: 0.931 AC: 4490 AN: 4824

European-Finnish (FIN) AF: 0.706 AC: 7456 AN: 10564

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52421 AN: 67972

Other (OTH) AF: 0.817 AC: 1721 AN: 2106

Alfa AF: 0.780 Hom.: 193827

Bravo AF: 0.780

Asia WGS AF: 0.888 AC: 3089 AN: 3478

EpiCase AF: 0.789

EpiControl AF: 0.789

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.8
DANN	Benign	0.77
PhyloP100		0.38
Mutation Taster		=99/1	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: rs704219; hg19: chr12-22354921; COSMIC: COSV53950727;