rs6990312

Variant names:

• chr8-109590088-G-T
• rs6990312
• NM_001099754.2:c.428-3926C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099754.2(SYBU):​c.428-3926C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 151,678 control chromosomes in the GnomAD database, including 10,292 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (10292 hom., cov: 31)
• Consequence: SYBU NM_001099754.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.725

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYBU	NM_001099754.2	c.428-3926C>A		intron_variant	Intron 3 of 6	ENST00000276646.14	NP_001093224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYBU	ENST00000276646.14	c.428-3926C>A		intron_variant	Intron 3 of 6	1	NM_001099754.2	ENSP00000276646.9
SYBU	ENST00000424158.6	c.443-3926C>A		intron_variant	Intron 5 of 8	1		ENSP00000415654.2

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43930 AN: 151568 Hom.: 10239 Cov.: 31

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.289

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.290 AC: 44059 AN: 151678 Hom.: 10292 Cov.: 31 AF XY: 0.288 AC XY: 21372 AN XY: 74094

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.0124

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.298

Alfa AF: 0.213 Hom.: 763

Bravo AF: 0.314

Asia WGS AF: 0.229 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.9
DANN	Benign	0.29

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

Other links and lift over

dbSNP: rs6990312; hg19: chr8-110602317;