Genetic Variant NM_001099754.2:c.1987A>G (chr8-109574911-T-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_001099754.2(SYBU):c.1987A>G(p.Thr663Ala) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

Publications

0 publications found

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 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=0.15350452).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099754.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYBU	NM_001099754.2	MANE Select	c.1987A>G	p.Thr663Ala	missense	Exon 7 of 7	NP_001093224.1	Q9NX95-1
SYBU	NM_001099744.2		c.1987A>G	p.Thr663Ala	missense	Exon 8 of 8	NP_001093214.1	Q9NX95-1
SYBU	NM_001099745.2		c.1987A>G	p.Thr663Ala	missense	Exon 8 of 8	NP_001093215.1	Q9NX95-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYBU	ENST00000276646.14	TSL:1 MANE Select	c.1987A>G	p.Thr663Ala	missense	Exon 7 of 7	ENSP00000276646.9	Q9NX95-1
SYBU	ENST00000424158.6	TSL:1	c.2002A>G	p.Thr668Ala	missense	Exon 9 of 9	ENSP00000415654.2	A0A0C4DG86
SYBU	ENST00000446070.6	TSL:1	c.1984A>G	p.Thr662Ala	missense	Exon 8 of 8	ENSP00000414748.2	Q9NX95-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1361228

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

665722

African (AFR)

AF:

0.00

AC:

AN:

30144

American (AMR)

AF:

0.00

AC:

AN:

28722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19814

East Asian (EAS)

AF:

0.00

AC:

AN:

38734

South Asian (SAS)

AF:

0.00

AC:

AN:

69592

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49788

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5284

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1063190

Other (OTH)

AF:

0.00

AC:

AN:

55960

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

Eigen

Benign

0.060

Eigen_PC

Benign

-0.031

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.72

M_CAP

Benign

0.0089

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.5

PhyloP100

1.7

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.58

REVEL

Benign

0.086

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.084

MutPred

0.27

Gain of helix (P = 0.062)

MVP

0.25

MPC

0.92

ClinPred

0.88

GERP RS

3.3

Varity_R

0.17

gMVP

0.32

Mutation Taster

=86/14

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over