1-114127153-C-T

Variant names:

• chr1-114127153-C-T
• rs4307568
• NM_001253772.2:c.1071+10342G>A

Variant summary

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

The NM_001253772.2(SYT6):​c.1071+10342G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,136 control chromosomes in the GnomAD database, including 4,904 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 0.25 (4904 hom., cov: 32)
• Consequence: SYT6 NM_001253772.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 3 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.263 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.1071+10342G>A		intron	N/A	NP_001240701.1	Q5T7P8-1
	SYT6	NM_001366224.1		c.1071+10342G>A		intron	N/A	NP_001353153.1	A0A7I2PMW4
	SYT6	NM_001366225.1		c.1071+10342G>A		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.1071+10342G>A		intron	N/A	ENSP00000476396.1	Q5T7P8-1
	SYT6	ENST00000369547.6	TSL:1	c.1071+10342G>A		intron	N/A	ENSP00000358560.2	A0A7I2PMW4
	SYT6	ENST00000610096.1	TSL:1	n.*772+10342G>A		intron	N/A	ENSP00000477325.1	V9GYB1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38182 AN: 152014 Hom.: 4896 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.251 AC: 38203 AN: 152136 Hom.: 4904 Cov.: 32 AF XY: 0.254 AC XY: 18872 AN XY: 74376

African (AFR) AF: 0.251 AC: 10405 AN: 41492

American (AMR) AF: 0.270 AC: 4129 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 832 AN: 3470

East Asian (EAS) AF: 0.233 AC: 1206 AN: 5174

South Asian (SAS) AF: 0.265 AC: 1278 AN: 4816

European-Finnish (FIN) AF: 0.292 AC: 3087 AN: 10586

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16578 AN: 67994

Other (OTH) AF: 0.234 AC: 494 AN: 2114

Alfa AF: 0.250 Hom.: 2952

Bravo AF: 0.249

Asia WGS AF: 0.234 AC: 817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.0060
DANN	Benign	0.64
PhyloP100		-1.7
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: rs4307568; hg19: chr1-114669775;