Genetic Variant SYT14:c.-610C>T (chr1-209938201-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000637265.1(SYT14):c.-610C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000469 in 1,478,348 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 2 hom. )

Consequence

SYT14
ENST00000637265.1 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.261

Publications

0 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: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet

SYT14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 1-209938201-C-T is Benign according to our data. Variant chr1-209938201-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1804620.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000637265.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYT14	NM_001146262.4	MANE Select	c.-64C>T	upstream_gene	N/A	NP_001139734.1	Q8NB59-6
SYT14	NM_001397544.1		c.-1113C>T	upstream_gene	N/A	NP_001384473.1	A0A8V8TN09
SYT14	NM_001397545.1		c.-1318C>T	upstream_gene	N/A	NP_001384474.1	A0A8V8TN09

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYT14	ENST00000637265.1	TSL:5	c.-610C>T	5_prime_UTR	Exon 1 of 10	ENSP00000489897.1	A0A1B0GTZ1
SYT14	ENST00000537238.5	TSL:5	c.-383C>T	5_prime_UTR	Exon 1 of 9	ENSP00000437423.1	Q8NB59-3
SYT14	ENST00000652023.1		n.52-14508C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00277

AC:

420

AN:

151552

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00977

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000855

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000962

GnomAD2 exomes

AF:

0.000365

AC:

AN:

134206

AF XY:

0.000204

show subpopulations

Gnomad AFR exome

AF:

0.00897

Gnomad AMR exome

AF:

0.000192

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000203

AC:

269

AN:

1326688

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

118

AN XY:

656568

show subpopulations

African (AFR)

AF:

0.00824

AC:

223

AN:

27062

American (AMR)

AF:

0.000226

AC:

AN:

30970

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22188

East Asian (EAS)

AF:

0.00

AC:

AN:

28502

South Asian (SAS)

AF:

0.0000534

AC:

AN:

74888

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47658

Middle Eastern (MID)

AF:

0.000196

AC:

AN:

5098

European-Non Finnish (NFE)

AF:

0.00000289

AC:

AN:

1037102

Other (OTH)

AF:

0.000582

AC:

AN:

53220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00280

AC:

425

AN:

151660

Hom.:

Cov.:

AF XY:

0.00286

AC XY:

212

AN XY:

74144

show subpopulations

African (AFR)

AF:

0.00986

AC:

409

AN:

41468

American (AMR)

AF:

0.000854

AC:

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67844

Other (OTH)

AF:

0.000951

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00143

Hom.:

Bravo

AF:

0.00309

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

0.26

PromoterAI

0.47

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over