chr1-210094548-TGAA-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 1P and 9B. PM4_SupportingBP6BA1

The NM_001146262.4(SYT14):c.675_677delAGA(p.Glu225del) variant causes a disruptive 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 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 9.35

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive spinocerebellar ataxia 11
Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

SYT14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 212360.

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 rank	MANE	Protein	UniProt
SYT14	NM_001146262.4 link	c.675_677delAGA	p.Glu225del	disruptive_inframe_deletion	Exon 5 of 9	ENST00000367019.6	NP_001139734.1	Q8NB59-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT14	ENST00000367019.6 link	c.675_677delAGA	p.Glu225del	disruptive_inframe_deletion	Exon 5 of 9	1	NM_001146262.4	ENSP00000355986.1		Q8NB59-6
SYT14	ENST00000534859.2 link	c.441_443delAGA	p.Glu147del	disruptive_inframe_deletion	Exon 2 of 6	1		ENSP00000442891.2		A0A0A0MTK4

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

GnomAD2 exomes

AF:

0.116

AC:

29060

AN:

249712

AF XY:

0.120

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 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

African (AFR)

AF:

0.0202

AC:

675

AN:

33468

American (AMR)

AF:

0.0601

AC:

2682

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.0707

AC:

1848

AN:

26132

East Asian (EAS)

AF:

0.102

AC:

4055

AN:

39686

South Asian (SAS)

AF:

0.121

AC:

10457

AN:

86244

European-Finnish (FIN)

AF:

0.214

AC:

11404

AN:

53348

Middle Eastern (MID)

AF:

0.0961

AC:

554

AN:

5766

European-Non Finnish (NFE)

AF:

0.139

AC:

154593

AN:

1111744

Other (OTH)

AF:

0.118

AC:

7150

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

9206

18412

27618

36824

46030

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5398

10796

16194

21592

26990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.102

AC:

15572

AN:

152160

Hom.:

1090

Cov.:

AF XY:

0.107

AC XY:

7943

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0247

AC:

1028

AN:

41536

American (AMR)

AF:

0.0763

AC:

1167

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0714

AC:

248

AN:

3472

East Asian (EAS)

AF:

0.0866

AC:

449

AN:

5182

South Asian (SAS)

AF:

0.129

AC:

624

AN:

4820

European-Finnish (FIN)

AF:

0.225

AC:

2379

AN:

10570

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.137

AC:

9306

AN:

67976

Other (OTH)

AF:

0.0900

AC:

190

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

690

1380

2071

2761

3451

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 28, 2019

Mendelics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Uncertain:1

Jul 15, 2014

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

9.4

Mutation Taster

=45/55

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over