1-114128347-A-G

Position:

• chr1-114128347-A-G

Variant summary

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

The NM_001253772.2(SYT6):​c.1071+9148T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 152,248 control chromosomes in the GnomAD database, including 52,336 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 0.83 (52336 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYT6	NM_001253772.2	c.1071+9148T>C		intron_variant		ENST00000610222.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT6	ENST00000610222.3	c.1071+9148T>C		intron_variant		5	NM_001253772.2	P1

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125694 AN: 152128 Hom.: 52284 Cov.: 33

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.821

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

GnomAD4 genome AF: 0.826 AC: 125806 AN: 152248 Hom.: 52336 Cov.: 33 AF XY: 0.833 AC XY: 62002 AN XY: 74428

Gnomad4 AFR AF: 0.914

Gnomad4 AMR AF: 0.860

Gnomad4 ASJ AF: 0.831

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.917

Gnomad4 FIN AF: 0.825

Gnomad4 NFE AF: 0.755

Gnomad4 OTH AF: 0.822

Alfa AF: 0.780 Hom.: 69106

Bravo AF: 0.829

Asia WGS AF: 0.920 AC: 3200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.46
DANN	Benign	0.53

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: rs2774307; hg19: chr1-114670969; COSMIC: COSV65773052;