Genetic Variant SYT10:c.509+2083T>G (chr12-33424055-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198992.4(SYT10):c.509+2083T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 454,176 control chromosomes in the GnomAD database, including 108,654 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.72 ( 40791 hom., cov: 32)

Exomes 𝑓: 0.66 ( 67863 hom. )

Consequence

SYT10
NM_198992.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.159

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT10	NM_198992.4 link	c.509+2083T>G		intron_variant	Intron 2 of 6	ENST00000228567.7	NP_945343.1	Q6XYQ8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYT10	ENST00000228567.7 link	c.509+2083T>G	intron_variant	Intron 2 of 6	1	NM_198992.4	ENSP00000228567.3	Q6XYQ8
SYT10	ENST00000539102.1 link	n.510-46T>G	intron_variant	Intron 2 of 8	1		ENSP00000444577.1	F5GZB8
SYT10	ENST00000567656.1 link	n.23+2083T>G	intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.717

AC:

108899

AN:

151920

Hom.:

40730

Cov.:

show subpopulations

Gnomad AFR

AF:

0.914

Gnomad AMI

AF:

0.728

Gnomad AMR

AF:

0.730

Gnomad ASJ

AF:

0.690

Gnomad EAS

AF:

0.949

Gnomad SAS

AF:

0.762

Gnomad FIN

AF:

0.579

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.596

Gnomad OTH

AF:

0.710

GnomAD2 exomes

AF:

0.697

AC:

88336

AN:

126718

AF XY:

0.693

show subpopulations

Gnomad AFR exome

AF:

0.924

Gnomad AMR exome

AF:

0.716

Gnomad ASJ exome

AF:

0.687

Gnomad EAS exome

AF:

0.953

Gnomad FIN exome

AF:

0.613

Gnomad NFE exome

AF:

0.599

Gnomad OTH exome

AF:

0.666

GnomAD4 exome

AF:

0.662

AC:

200030

AN:

302140

Hom.:

67863

Cov.:

AF XY:

0.666

AC XY:

114632

AN XY:

172106

show subpopulations

Gnomad4 AFR exome

AF:

0.919

AC:

7835

AN:

8530

Gnomad4 AMR exome

AF:

0.716

AC:

19342

AN:

27010

Gnomad4 ASJ exome

AF:

0.684

AC:

7323

AN:

10704

Gnomad4 EAS exome

AF:

0.951

AC:

8735

AN:

9188

Gnomad4 SAS exome

AF:

0.726

AC:

43168

AN:

59424

Gnomad4 FIN exome

AF:

0.618

AC:

7610

AN:

12312

Gnomad4 NFE exome

AF:

0.600

AC:

94846

AN:

158092

Gnomad4 Remaining exome

AF:

0.668

AC:

9424

AN:

14116

Heterozygous variant carriers

3265

6530

9796

13061

16326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

598

1196

1794

2392

2990

<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:

0.717

AC:

109015

AN:

152036

Hom.:

40791

Cov.:

AF XY:

0.720

AC XY:

53490

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.914

AC:

0.913964

AN:

0.913964

Gnomad4 AMR

AF:

0.729

AC:

0.729489

AN:

0.729489

Gnomad4 ASJ

AF:

0.690

AC:

0.689625

AN:

0.689625

Gnomad4 EAS

AF:

0.949

AC:

0.949208

AN:

0.949208

Gnomad4 SAS

AF:

0.760

AC:

0.760174

AN:

0.760174

Gnomad4 FIN

AF:

0.579

AC:

0.579311

AN:

0.579311

Gnomad4 NFE

AF:

0.596

AC:

0.596034

AN:

0.596034

Gnomad4 OTH

AF:

0.715

AC:

0.714692

AN:

0.714692

Heterozygous variant carriers

1407

2814

4220

5627

7034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

820

1640

2460

3280

4100

<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:

0.654

Hom.:

49828

Bravo

AF:

0.735

Asia WGS

AF:

0.866

AC:

3008

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

5.7

DANN

Benign

0.76

Mutation Taster

=100/0

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over