Genetic Variant NM_003896.4:c.37C>G (chr2-85888869-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003896.4(ST3GAL5):c.37C>G(p.Pro13Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000247 in 1,214,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. P13S) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000025 ( 0 hom. )

Consequence

ST3GAL5
NM_003896.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.114

Publications

0 publications found

Variant links:

Genes affected

ST3GAL5 (HGNC:10872): (ST3 beta-galactoside alpha-2,3-sialyltransferase 5) Ganglioside GM3 is known to participate in the induction of cell differentiation, modulation of cell proliferation, maintenance of fibroblast morphology, signal transduction, and integrin-mediated cell adhesion. The protein encoded by this gene is a type II membrane protein which catalyzes the formation of GM3 using lactosylceramide as the substrate. The encoded protein is a member of glycosyltransferase family 29 and may be localized to the Golgi apparatus. Mutation in this gene has been associated with Amish infantile epilepsy syndrome. Transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ST3GAL5 Gene-Disease associations (from GenCC):

GM3 synthase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ST3GAL5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10032201).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL5	NM_003896.4 link	c.37C>G	p.Pro13Ala	missense_variant	Exon 1 of 7	ENST00000638572.2	NP_003887.3	Q9UNP4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST3GAL5	ENST00000638572.2 link	c.37C>G	p.Pro13Ala	missense_variant	Exon 1 of 7	1	NM_003896.4	ENSP00000491316.1		Q9UNP4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000247

AC:

AN:

1214820

Hom.:

Cov.:

AF XY:

0.00000335

AC XY:

AN XY:

596522

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24926

American (AMR)

AF:

0.00

AC:

AN:

22320

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19792

East Asian (EAS)

AF:

0.00

AC:

AN:

24712

South Asian (SAS)

AF:

0.00

AC:

AN:

58092

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28738

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3344

European-Non Finnish (NFE)

AF:

0.00000305

AC:

AN:

984682

Other (OTH)

AF:

0.00

AC:

AN:

48214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.26

T;.;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.65

T;T;T

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.;.

PhyloP100

0.11

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.98

.;N;.

REVEL

Benign

0.041

Sift

Pathogenic

0.0

.;D;.

Sift4G

Pathogenic

0.0

.;D;.

Polyphen

0.0

B;.;.

Vest4

0.16

MutPred

0.13

Gain of helix (P = 0.005);Gain of helix (P = 0.005);Gain of helix (P = 0.005);

MVP

0.095

MPC

0.30

ClinPred

0.10

GERP RS

1.2

PromoterAI

0.022

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.14

Mutation Taster

=95/5

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over