dbSNP rs368545452: SYT14:c.-13T>C (chr1-209938252-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PVS1_Supporting

The NM_001146261.4(SYT14):c.2T>C(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000571 in 1,558,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

SYT14
NM_001146261.4 start_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.173

Publications

1 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: Uncertain_significance. The variant received 1 ACMG points.

PVS1

Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 18 codons. Genomic position: 209952733. Lost 0.028 part of the original CDS.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146261.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYT14	NM_001146262.4	MANE Select	c.-13T>C		5_prime_UTR	Exon 1 of 9	NP_001139734.1	Q8NB59-6
SYT14	NM_001146261.4		c.2T>C	p.Met1?	start_lost	Exon 1 of 10	NP_001139733.1	Q8NB59-7
SYT14	NM_001146264.4		c.2T>C	p.Met1?	start_lost	Exon 1 of 9	NP_001139736.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYT14	ENST00000367019.6	TSL:1 MANE Select	c.-13T>C	5_prime_UTR	Exon 1 of 9	ENSP00000355986.1	Q8NB59-6
SYT14	ENST00000472886.5	TSL:1	c.-13T>C	5_prime_UTR	Exon 1 of 8	ENSP00000418901.1	Q8NB59-1
SYT14	ENST00000637945.1	TSL:1	n.-13T>C	non_coding_transcript_exon	Exon 1 of 10	ENSP00000489671.1	A0A1B0GTF1

Frequencies

GnomAD3 genomes

AF:

0.000290

AC:

AN:

151510

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000475

AC:

AN:

210522

AF XY:

0.0000433

show subpopulations

Gnomad AFR exome

AF:

0.000636

Gnomad AMR exome

AF:

0.0000333

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000209

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000320

AC:

AN:

1406732

Hom.:

Cov.:

AF XY:

0.0000300

AC XY:

AN XY:

699484

show subpopulations

African (AFR)

AF:

0.000271

AC:

AN:

29476

American (AMR)

AF:

0.0000248

AC:

AN:

40350

Ashkenazi Jewish (ASJ)

AF:

0.0000414

AC:

AN:

24160

East Asian (EAS)

AF:

0.00

AC:

AN:

34520

South Asian (SAS)

AF:

0.00

AC:

AN:

81560

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5550

European-Non Finnish (NFE)

AF:

0.0000287

AC:

AN:

1081812

Other (OTH)

AF:

0.0000697

AC:

AN:

57354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.000290

AC:

AN:

151616

Hom.:

Cov.:

AF XY:

0.000351

AC XY:

AN XY:

74134

show subpopulations

African (AFR)

AF:

0.00101

AC:

AN:

41460

American (AMR)

AF:

0.000131

AC:

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10366

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67828

Other (OTH)

AF:

0.00

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000133

Hom.:

Bravo

AF:

0.000238

ESP6500AA

AF:

0.000914

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000914

AC:

Asia WGS

AF:

0.000589

AC:

AN:

3412

ClinVar

ClinVar submissions

Significance:Uncertain significance

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_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.78

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.024

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.080

MetaSVM

Benign

-1.0

PhyloP100

0.17

Vest4

0.54

MVP

0.043

ClinPred

0.59

GERP RS

2.7

PromoterAI

-0.11

Neutral

(source)

gMVP

0.24

Mutation Taster

=85/115

disease causing (ClinVar)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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