8-109575112-C-T

Variant names:

• chr8-109575112-C-T
• rs1188965237
• NM_001099754.2:c.1786G>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.1786G>A​(p.Gly596Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SYBU NM_001099754.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.27
• 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=0.113334864).

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.1786G>A	p.Gly596Arg	missense	Exon 7 of 7	NP_001093224.1	Q9NX95-1
	SYBU	NM_001099744.2		c.1786G>A	p.Gly596Arg	missense	Exon 8 of 8	NP_001093214.1	Q9NX95-1
	SYBU	NM_001099745.2		c.1786G>A	p.Gly596Arg	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.1786G>A	p.Gly596Arg	missense	Exon 7 of 7	ENSP00000276646.9	Q9NX95-1
	SYBU	ENST00000424158.6	TSL:1	c.1801G>A	p.Gly601Arg	missense	Exon 9 of 9	ENSP00000415654.2	A0A0C4DG86
	SYBU	ENST00000446070.6	TSL:1	c.1783G>A	p.Gly595Arg	missense	Exon 8 of 8	ENSP00000414748.2	Q9NX95-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000804 AC: 2 AN: 248688 AF XY: 0.00000741

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460840 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726582

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111272

Other (OTH) AF: 0.00 AC: 0 AN: 60340

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74352

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.3
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.051
Sift	Uncertain	0.013	D
Sift4G	Benign	0.066	T
Polyphen		0.099	B
Vest4		0.11
MutPred		0.53		Gain of solvent accessibility (P = 0.0097)
MVP		0.30
MPC		0.32
ClinPred		0.16	T
GERP RS		4.0
Varity_R		0.11
gMVP		0.47
Mutation Taster		=85/15	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: rs1188965237; hg19: chr8-110587341;