1-114128347-A-G

Variant names:

• chr1-114128347-A-G
• rs2774307
• NM_001253772.2:c.1071+9148T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366224.1(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_001366224.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366224.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT6	NM_001253772.2	MANE Select	c.1071+9148T>C		intron	N/A	NP_001240701.1
	SYT6	NM_001366224.1		c.1071+9148T>C		intron	N/A	NP_001353153.1
	SYT6	NM_001366225.1		c.1071+9148T>C		intron	N/A	NP_001353154.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT6	ENST00000610222.3	TSL:5 MANE Select	c.1071+9148T>C		intron	N/A	ENSP00000476396.1
	SYT6	ENST00000369547.6	TSL:1	c.1071+9148T>C		intron	N/A	ENSP00000358560.2
	SYT6	ENST00000610096.1	TSL:1	n.*772+9148T>C		intron	N/A	ENSP00000477325.1

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

African (AFR) AF: 0.914 AC: 37989 AN: 41550

American (AMR) AF: 0.860 AC: 13158 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2885 AN: 3470

East Asian (EAS) AF: 0.898 AC: 4651 AN: 5180

South Asian (SAS) AF: 0.917 AC: 4424 AN: 4822

European-Finnish (FIN) AF: 0.825 AC: 8753 AN: 10606

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.755 AC: 51315 AN: 67996

Other (OTH) AF: 0.822 AC: 1740 AN: 2116

Alfa AF: 0.783 Hom.: 95573

Bravo AF: 0.829

Asia WGS AF: 0.920 AC: 3200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.46
DANN	Benign	0.53
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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