12-33382460-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_198992.4(SYT10):c.1259C>G(p.Thr420Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000592 in 1,612,990 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0034 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 6 hom. )

Consequence

SYT10
NM_198992.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 9.24

Publications

2 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008290082).

BP6

Variant 12-33382460-G-C is Benign according to our data. Variant chr12-33382460-G-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 714177. Variant chr12-33382460-G-C is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 714177.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT10	NM_198992.4 link	c.1259C>G	p.Thr420Ser	missense_variant	Exon 5 of 7	ENST00000228567.7	NP_945343.1	Q6XYQ8
SYT10	XM_011520644.4 link	c.716C>G	p.Thr239Ser	missense_variant	Exon 4 of 6		XP_011518946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYT10	ENST00000228567.7 link	c.1259C>G	p.Thr420Ser	missense_variant	Exon 5 of 7	1	NM_198992.4	ENSP00000228567.3	Q6XYQ8
SYT10	ENST00000539102.1 link	n.*854C>G		non_coding_transcript_exon_variant	Exon 7 of 9	1		ENSP00000444577.1	F5GZB8
SYT10	ENST00000539102.1 link	n.*854C>G		3_prime_UTR_variant	Exon 7 of 9	1		ENSP00000444577.1	F5GZB8

Frequencies

GnomAD3 genomes

AF:

0.00337

AC:

512

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0117

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

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:

0.0000147

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.000783

AC:

196

AN:

250442

AF XY:

0.000606

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.000818

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.000299

AC:

437

AN:

1460730

Hom.:

Cov.:

AF XY:

0.000227

AC XY:

165

AN XY:

726684

show subpopulations

African (AFR)

AF:

0.0104

AC:

348

AN:

33396

American (AMR)

AF:

0.000875

AC:

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39632

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86134

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111420

Other (OTH)

AF:

0.000779

AC:

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00340

AC:

518

AN:

152260

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

241

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0118

AC:

491

AN:

41570

American (AMR)

AF:

0.00124

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67998

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

100

125

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:

0.000475

Hom.:

Bravo

AF:

0.00332

ESP6500AA

AF:

0.00953

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000988

AC:

120

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 17, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.078

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.12

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0083

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.36

PhyloP100

9.2

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.15

REVEL

Benign

0.27

Sift

Benign

0.89

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.20

MutPred

0.20

Gain of catalytic residue at K422 (P = 0.0183);

MVP

0.61

MPC

0.15

ClinPred

0.065

GERP RS

4.0

Varity_R

0.11

gMVP

0.21

Mutation Taster

=87/13

polymorphism

(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

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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