Genetic Variant ST8SIA1:p.Leu352Pro (chr12-22201568-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003034.4(ST8SIA1):c.1055T>C(p.Leu352Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L352H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ST8SIA1
NM_003034.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.568

Publications

0 publications found

Variant links:

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]

ST8SIA1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039941818).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST8SIA1	NM_003034.4 link	c.1055T>C	p.Leu352Pro	missense_variant	Exon 5 of 5	ENST00000396037.9	NP_003025.1	Q92185-1
ST8SIA1	NM_001304450.2 link	c.626T>C	p.Leu209Pro	missense_variant	Exon 4 of 4		NP_001291379.1	Q92185

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST8SIA1	ENST00000396037.9 link	c.1055T>C	p.Leu352Pro	missense_variant	Exon 5 of 5	1	NM_003034.4	ENSP00000379353.3		Q92185-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000405

AC:

AN:

246872

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000897

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457594

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724812

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33424

American (AMR)

AF:

0.00

AC:

AN:

44454

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25682

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

85334

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53224

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5552

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1110002

Other (OTH)

AF:

0.00

AC:

AN:

60234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

9.0

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.078

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.45

M_CAP

Benign

0.0066

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.57

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.62

REVEL

Benign

0.036

Sift

Benign

0.17

Sift4G

Benign

0.27

Polyphen

0.0

Vest4

0.13

MutPred

0.14

Gain of disorder (P = 0.0521);

MVP

0.10

MPC

0.69

ClinPred

0.032

GERP RS

0.51

Varity_R

0.050

gMVP

0.54

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over