Genetic Variant SYT12:p.Ala26Val (chr11-67034687-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_177963.4(SYT12):c.77C>T(p.Ala26Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A26S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SYT12
NM_177963.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.51

Publications

0 publications found

Variant links:

Genes affected

SYT12 (HGNC:18381): (synaptotagmin 12) This gene is a member of the synaptotagmin gene family and encodes a protein similar to other family members that mediate calcium-dependent regulation of membrane trafficking in synaptic transmission. Studies of the orthologous gene in rat have shown that the encoded protein selectively modulates spontaneous synaptic-vesicle exocytosis and may also be involved in regulating calcium independent secretion in nonneuronal cells. Alternative splicing results in multiple transcript variants. The gene has previously been referred to as synaptotagmin XI but has been renamed synaptotagmin XII to be standard with mouse and rat official nomenclature.[provided by RefSeq, Apr 2010]

SYT12 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11212617).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177963.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYT12	NM_177963.4	MANE Select	c.77C>T	p.Ala26Val	missense	Exon 3 of 8	NP_808878.1	Q8IV01
SYT12	NM_001177880.2		c.77C>T	p.Ala26Val	missense	Exon 3 of 8	NP_001171351.1	Q8IV01
SYT12	NM_001318773.2		c.-269C>T		5_prime_UTR	Exon 4 of 9	NP_001305702.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYT12	ENST00000527043.6	TSL:1 MANE Select	c.77C>T	p.Ala26Val	missense	Exon 3 of 8	ENSP00000435316.1	Q8IV01
SYT12	ENST00000393946.6	TSL:2	c.77C>T	p.Ala26Val	missense	Exon 6 of 11	ENSP00000377520.2	Q8IV01
SYT12	ENST00000525457.5	TSL:2	c.77C>T	p.Ala26Val	missense	Exon 3 of 8	ENSP00000431400.1	Q8IV01

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1450250

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721454

African (AFR)

AF:

0.00

AC:

AN:

32710

American (AMR)

AF:

0.00

AC:

AN:

42396

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25858

East Asian (EAS)

AF:

0.00

AC:

AN:

38700

South Asian (SAS)

AF:

0.00

AC:

AN:

84220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53236

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107480

Other (OTH)

AF:

0.00

AC:

AN:

59912

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0029

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.20

PhyloP100

4.5

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.0

REVEL

Benign

0.077

Sift

Benign

0.15

Sift4G

Benign

0.20

Polyphen

0.010

Vest4

0.26

MutPred

0.27

Loss of helix (P = 0.3949)

MVP

0.092

MPC

0.16

ClinPred

0.61

GERP RS

4.9

Varity_R

0.12

gMVP

0.46

Mutation Taster

=74/26

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over