rs529989

chr1-114135326-C-Achr1-114135326-C-Gchr1-114135326-C-T

Variant summary

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

The NM_001253772.2(SYT6):c.1071+2169G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 151,900 control chromosomes in the GnomAD database, including 26,841 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 0.59 (26841 hom., cov: 31)
• Consequence: SYT6 NM_001253772.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

Genes affected

SYT6 (HGNC:18638): (synaptotagmin 6) The protein encoded by this gene belongs to the synaptotagmin family. Synaptotagmins share a common domain structure that includes a transmembrane domain and a cytoplasmic region composed of 2 C2 domains, and are involved in calcium-dependent exocytosis of synaptic vesicles. This protein has been shown to be a key component of the secretory machinery involved in acrosomal exocytosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYT6	NM_001253772.2	c.1071+2169G>T		intron_variant		ENST00000610222.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT6	ENST00000610222.3	c.1071+2169G>T		intron_variant		5	NM_001253772.2	P1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89834 AN: 151782 Hom.: 26828 Cov.: 31

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.592 AC: 89894 AN: 151900 Hom.: 26841 Cov.: 31 AF XY: 0.598 AC XY: 44422 AN XY: 74234

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.767

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.592

Alfa AF: 0.564 Hom.: 32352

Bravo AF: 0.590

Asia WGS AF: 0.713 AC: 2476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.067
Dann	Benign	0.38

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: rs529989; hg19: chr1-114677948;