dbSNP rs762659962: SYBU:p.Val618Leu (chr8-109575046-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001099754.2(SYBU):c.1852G>C(p.Val618Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 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. V618M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SYBU
NM_001099754.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.732

Variant links:

Genes affected

SYBU (HGNC:26011): (syntabulin) Syntabulin/GOLSYN is part of a kinesin motor-adaptor complex that is critical for the anterograde axonal transport of active zone components and contributes to activity-dependent presynaptic assembly during neuronal development (Cai et al., 2007 [PubMed 17611281]).[supplied by OMIM, Mar 2008]

SYBU links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14259186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYBU	NM_001099754.2 link	c.1852G>C	p.Val618Leu	missense_variant	Exon 7 of 7	ENST00000276646.14	NP_001093224.1	Q9NX95-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYBU	ENST00000276646.14 link	c.1852G>C	p.Val618Leu	missense_variant	Exon 7 of 7	1	NM_001099754.2	ENSP00000276646.9		Q9NX95-1
SYBU	ENST00000424158.6 link	c.1867G>C	p.Val623Leu	missense_variant	Exon 9 of 9	1		ENSP00000415654.2		A0A0C4DG86

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000409

AC:

AN:

244602

Hom.:

AF XY:

0.00000755

AC XY:

AN XY:

132512

show subpopulations

Gnomad AFR exome

AF:

0.0000649

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1455726

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723320

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.074

.;T;.;.;.;.;.;T;.;T;T;T;.;T;.;T;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.81

.;T;T;T;.;.;T;.;T;.;.;T;T;.;.;T;.

M_CAP

Benign

0.0047

MetaRNN

Benign

0.14

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

.;.;.;.;.;.;.;M;.;M;M;M;.;M;.;.;M

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.3

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.041

Sift

Benign

0.090

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.26

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.54

P;.;B;P;P;.;.;P;P;P;P;P;.;P;.;B;P

Vest4

0.14

MutPred

0.40

.;.;.;.;.;.;.;Loss of catalytic residue at V618 (P = 0.1278);.;Loss of catalytic residue at V618 (P = 0.1278);Loss of catalytic residue at V618 (P = 0.1278);Loss of catalytic residue at V618 (P = 0.1278);.;Loss of catalytic residue at V618 (P = 0.1278);.;.;Loss of catalytic residue at V618 (P = 0.1278);

MVP

0.18

MPC

0.30

ClinPred

0.092

GERP RS

2.9

Varity_R

0.066

gMVP

0.71

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over