Variant 12-33376853-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_198992.4(SYT10):c.1549C>G(p.Pro517Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000335 in 1,614,092 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 2 hom. )

Consequence

SYT10
NM_198992.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.19

Variant links:

Genes affected

SYT10 (HGNC:19266): (synaptotagmin 10) Predicted to enable several functions, including phospholipid binding activity; protein dimerization activity; and syntaxin binding activity. Predicted to be involved in several processes, including cellular response to calcium ion; regulation of secretion by cell; and sensory perception of smell. Predicted to be located in synapse and transport vesicle membrane. Predicted to be integral component of membrane. Predicted to be active in exocytic vesicle and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SYT10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019731075).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT10	NM_198992.4 link	c.1549C>G	p.Pro517Ala	missense_variant	Exon 7 of 7	ENST00000228567.7	NP_945343.1	Q6XYQ8
SYT10	XM_011520644.4 link	c.1006C>G	p.Pro336Ala	missense_variant	Exon 6 of 6		XP_011518946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYT10	ENST00000228567.7 link	c.1549C>G	p.Pro517Ala	missense_variant	Exon 7 of 7	1	NM_198992.4	ENSP00000228567.3	Q6XYQ8
SYT10	ENST00000539102.1 link	n.*1144C>G		non_coding_transcript_exon_variant	Exon 9 of 9	1		ENSP00000444577.1	F5GZB8
SYT10	ENST00000539102.1 link	n.*1144C>G		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000444577.1	F5GZB8

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000438

AC:

110

AN:

251240

Hom.:

AF XY:

0.000420

AC XY:

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000299

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000335

AC:

490

AN:

1461818

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

234

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000349

Gnomad4 OTH exome

AF:

0.000397

GnomAD4 genome

AF:

0.000328

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000345

Hom.:

Bravo

AF:

0.000480

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000362

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 18, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1549C>G (p.P517A) alteration is located in exon 7 (coding exon 7) of the SYT10 gene. This alteration results from a C to G substitution at nucleotide position 1549, causing the proline (P) at amino acid position 517 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.0090

MetaRNN

Benign

0.020

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.3

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.3

REVEL

Benign

0.12

Sift

Benign

0.51

Sift4G

Benign

0.42

Polyphen

0.10

Vest4

0.58

MVP

0.54

MPC

0.63

ClinPred

0.67

GERP RS

4.7

Varity_R

0.10

gMVP

0.44

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

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