rs1119040

Positions:

• chr1-114141797-G-A

Variant summary

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

The NM_001253772.2(SYT6):​c.164-1834C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,120 control chromosomes in the GnomAD database, including 3,586 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 0.21 (3586 hom., cov: 33)
• Consequence: SYT6 NM_001253772.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT6	NM_001253772.2	c.164-1834C>T		intron_variant		ENST00000610222.3	NP_001240701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYT6	ENST00000610222.3	c.164-1834C>T		intron_variant		5	NM_001253772.2	ENSP00000476396.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31466 AN: 152002 Hom.: 3578 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.207 AC: 31499 AN: 152120 Hom.: 3586 Cov.: 33 AF XY: 0.219 AC XY: 16274 AN XY: 74338

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.208

Alfa AF: 0.200 Hom.: 4858

Bravo AF: 0.199

Asia WGS AF: 0.348 AC: 1210 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	0.22
DANN	Benign	0.19

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: rs1119040; hg19: chr1-114684419;