Variant 1-210094548-TGAA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PM4_SupportingBP6BA1

The NM_001146262.4(SYT14):c.675_677del(p.Glu225del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,613,578 control chromosomes in the GnomAD database, including 14,767 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.10 ( 1090 hom., cov: 31)

Exomes 𝑓: 0.13 ( 13677 hom. )

Consequence

SYT14
NM_001146262.4 inframe_deletion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 9.35

Variant links:

Genes affected

SYT14 (HGNC:23143): (synaptotagmin 14) This gene is a member of the synaptotagmin gene family and encodes a protein similar to other family members that mediate membrane trafficking in synaptic transmission. The encoded protein is a calcium-independent synaptotagmin. Mutations in this gene are a cause of autosomal recessive spinocerebellar ataxia-11 (SCAR11), and a t(1;3) translocation of this gene has been associated with neurodevelopmental abnormalities. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 4. [provided by RefSeq, Dec 2011]

SYT14 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001146262.4. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 1-210094548-TGAA-T is Benign according to our data. Variant chr1-210094548-TGAA-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 212360.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=2, Uncertain_significance=1}. Variant chr1-210094548-TGAA-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT14	NM_001146262.4 linkuse as main transcript	c.675_677del	p.Glu225del	inframe_deletion	5/9	ENST00000367019.6	NP_001139734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYT14	ENST00000367019.6 linkuse as main transcript	c.675_677del	p.Glu225del	inframe_deletion	5/9	1	NM_001146262.4	ENSP00000355986		Q8NB59-6

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15575

AN:

152042

Hom.:

1091

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0248

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.0764

Gnomad ASJ

AF:

0.0714

Gnomad EAS

AF:

0.0866

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.0909

GnomAD3 exomes

AF:

0.116

AC:

29060

AN:

249712

Hom.:

2042

AF XY:

0.120

AC XY:

16241

AN XY:

135062

show subpopulations

Gnomad AFR exome

AF:

0.0218

Gnomad AMR exome

AF:

0.0564

Gnomad ASJ exome

AF:

0.0691

Gnomad EAS exome

AF:

0.0755

Gnomad SAS exome

AF:

0.120

Gnomad FIN exome

AF:

0.217

Gnomad NFE exome

AF:

0.139

Gnomad OTH exome

AF:

0.120

GnomAD4 exome

AF:

0.132

AC:

193418

AN:

1461418

Hom.:

13677

AF XY:

0.133

AC XY:

96390

AN XY:

726994

show subpopulations

Gnomad4 AFR exome

AF:

0.0202

Gnomad4 AMR exome

AF:

0.0601

Gnomad4 ASJ exome

AF:

0.0707

Gnomad4 EAS exome

AF:

0.102

Gnomad4 SAS exome

AF:

0.121

Gnomad4 FIN exome

AF:

0.214

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.118

GnomAD4 genome

AF:

0.102

AC:

15572

AN:

152160

Hom.:

1090

Cov.:

AF XY:

0.107

AC XY:

7943

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0247

Gnomad4 AMR

AF:

0.0763

Gnomad4 ASJ

AF:

0.0714

Gnomad4 EAS

AF:

0.0866

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.225

Gnomad4 NFE

AF:

0.137

Gnomad4 OTH

AF:

0.0900

Alfa

AF:

0.113

Hom.:

224

Bravo

AF:

0.0875

Asia WGS

AF:

0.0840

AC:

294

AN:

3478

EpiCase

AF:

0.132

EpiControl

AF:

0.135

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Autosomal recessive spinocerebellar ataxia 11

Benign:3

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 15, 2014

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over