11-45283644-C-T

Variant names:

• chr11-45283644-C-T
• rs2289448
• NM_020826.3:c.183+2381G>A

Variant summary

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

The NM_020826.3(SYT13):​c.183+2381G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 152,128 control chromosomes in the GnomAD database, including 28,749 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 0.60 (28749 hom., cov: 33)
• Consequence: SYT13 NM_020826.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.784
• Publications: 0 publications found

Genes affected

SYT13 (HGNC:14962): (synaptotagmin 13) This gene encodes a member of the large synaptotagmin protein family. Family members have an extracellular N-terminal transmembrane domain and a cytoplasmic C terminus with two tandem C2 domains (C2A and C2B). Synaptotogmin family members can form homo- and heteromeric complexes with each other. They also have different biochemical properties and developmental profiles, and patterns of tissue distribution. Synaptotagmins function as membrane traffickers in multicellular organisms. Two alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020826.3. 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
	SYT13	NM_020826.3	MANE Select	c.183+2381G>A		intron	N/A	NP_065877.1	Q7L8C5
	SYT13	NM_001247987.2		c.-468+2381G>A		intron	N/A	NP_001234916.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT13	ENST00000020926.8	TSL:1 MANE Select	c.183+2381G>A		intron	N/A	ENSP00000020926.3	Q7L8C5
	SYT13	ENST00000533332.1	TSL:1	n.42+2381G>A		intron	N/A	ENSP00000434967.1	H0YE47
	SYT13	ENST00000528101.1	TSL:4	c.60+2219G>A		intron	N/A	ENSP00000432975.1	H0YD47

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91631 AN: 152010 Hom.: 28734 Cov.: 33

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.603 AC: 91680 AN: 152128 Hom.: 28749 Cov.: 33 AF XY: 0.605 AC XY: 44949 AN XY: 74342

African (AFR) AF: 0.417 AC: 17300 AN: 41472

American (AMR) AF: 0.711 AC: 10883 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2211 AN: 3468

East Asian (EAS) AF: 0.740 AC: 3826 AN: 5170

South Asian (SAS) AF: 0.575 AC: 2772 AN: 4820

European-Finnish (FIN) AF: 0.638 AC: 6748 AN: 10574

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45897 AN: 68006

Other (OTH) AF: 0.600 AC: 1270 AN: 2116

Alfa AF: 0.641 Hom.: 6657

Bravo AF: 0.605

Asia WGS AF: 0.602 AC: 2094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.63
PhyloP100		0.78
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: rs2289448; hg19: chr11-45305195;