NM_001099754.2:c.1880G>A

Variant names:

• chr8-109575018-C-T
• rs377692434
• NM_001099754.2:c.1880G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099754.2(SYBU):​c.1880G>A​(p.Ser627Asn) 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. 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. S627T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYBU NM_001099754.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54
• Publications: 0 publications found

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]

ACMG classification

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=0.1811235).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYBU	NM_001099754.2	MANE Select	c.1880G>A	p.Ser627Asn	missense	Exon 7 of 7	NP_001093224.1	Q9NX95-1
	SYBU	NM_001099744.2		c.1880G>A	p.Ser627Asn	missense	Exon 8 of 8	NP_001093214.1	Q9NX95-1
	SYBU	NM_001099745.2		c.1880G>A	p.Ser627Asn	missense	Exon 8 of 8	NP_001093215.1	Q9NX95-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYBU	ENST00000276646.14	TSL:1 MANE Select	c.1880G>A	p.Ser627Asn	missense	Exon 7 of 7	ENSP00000276646.9	Q9NX95-1
	SYBU	ENST00000424158.6	TSL:1	c.1895G>A	p.Ser632Asn	missense	Exon 9 of 9	ENSP00000415654.2	A0A0C4DG86
	SYBU	ENST00000446070.6	TSL:1	c.1877G>A	p.Ser626Asn	missense	Exon 8 of 8	ENSP00000414748.2	Q9NX95-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000120 AC: 1

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.034	T
Eigen	Benign	0.078
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.60	N
REVEL	Uncertain	0.30
Sift	Benign	0.22	T
Sift4G	Benign	0.77	T
Polyphen		0.16	B
Vest4		0.24
MVP		0.17
MPC		0.27
ClinPred		0.36	T
GERP RS		5.7
Varity_R		0.11
gMVP		0.62
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs377692434; hg19: chr8-110587247;