rs1119040

Variant names:

• chr1-114141797-G-A
• rs1119040
• NM_001253772.2:c.164-1834C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001253772.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT6	NM_001253772.2	MANE Select	c.164-1834C>T		intron	N/A	NP_001240701.1	Q5T7P8-1
	SYT6	NM_001366224.1		c.164-1834C>T		intron	N/A	NP_001353153.1	A0A7I2PMW4
	SYT6	NM_001366225.1		c.164-1834C>T		intron	N/A	NP_001353154.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT6	ENST00000610222.3	TSL:5 MANE Select	c.164-1834C>T		intron	N/A	ENSP00000476396.1	Q5T7P8-1
	SYT6	ENST00000369547.6	TSL:1	c.164-1834C>T		intron	N/A	ENSP00000358560.2	A0A7I2PMW4
	SYT6	ENST00000610096.1	TSL:1	n.164-1917C>T		intron	N/A	ENSP00000477325.1	V9GYB1

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

African (AFR) AF: 0.144 AC: 5987 AN: 41510

American (AMR) AF: 0.277 AC: 4232 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 539 AN: 3466

East Asian (EAS) AF: 0.307 AC: 1589 AN: 5180

South Asian (SAS) AF: 0.332 AC: 1601 AN: 4818

European-Finnish (FIN) AF: 0.320 AC: 3378 AN: 10548

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13509 AN: 67996

Other (OTH) AF: 0.208 AC: 440 AN: 2112

Alfa AF: 0.202 Hom.: 12455

Bravo AF: 0.199

Asia WGS AF: 0.348 AC: 1210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.19
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: rs1119040; hg19: chr1-114684419;