chr12-22255296-C-T

Variant names:

• chr12-22255296-C-T
• rs375737160
• NM_003034.4:c.475G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_003034.4(ST8SIA1):​c.475G>A​(p.Ala159Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000157 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: ST8SIA1 NM_003034.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.41
• Publications: 1 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.36925197).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA1	NM_003034.4	MANE Select	c.475G>A	p.Ala159Thr	missense	Exon 3 of 5	NP_003025.1	Q92185-1
	ST8SIA1	NM_001304450.2		c.63-6198G>A		intron	N/A	NP_001291379.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA1	ENST00000396037.9	TSL:1 MANE Select	c.475G>A	p.Ala159Thr	missense	Exon 3 of 5	ENSP00000379353.3	Q92185-1
	ST8SIA1	ENST00000261197.7	TSL:1	n.382-6198G>A		intron	N/A	ENSP00000261197.3	Q92185-2
	ST8SIA1	ENST00000540824.5	TSL:4	c.328G>A	p.Ala110Thr	missense	Exon 3 of 5	ENSP00000441707.1	H0YG41

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000477 AC: 12 AN: 251372 AF XY: 0.0000589

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000968

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000164 AC: 240 AN: 1461842 Hom.: 0 Cov.: 31 AF XY: 0.000161 AC XY: 117 AN XY: 727224

African (AFR) AF: 0.000119 AC: 4 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000208 AC: 231 AN: 1111968

Other (OTH) AF: 0.0000828 AC: 5 AN: 60394

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74388

African (AFR) AF: 0.0000482 AC: 2 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000580 Hom.: 0

Bravo AF: 0.0000718

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	0.0045	T
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.4
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.031	D
Polyphen		0.46	P
Vest4		0.91
MVP		0.55
MPC		0.97
ClinPred		0.33	T
GERP RS		5.8
Varity_R		0.27
gMVP		0.70
Mutation Taster		=42/58	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs375737160; hg19: chr12-22408230;