12-33424055-A-C

Position:

• chr12-33424055-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SYT10	NM_198992.4	c.509+2083T>G		intron_variant		ENST00000228567.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT10	ENST00000228567.7	c.509+2083T>G		intron_variant		1	NM_198992.4	P1
SYT10	ENST00000539102.1	c.510-46T>G		intron_variant, NMD_transcript_variant		1
SYT10	ENST00000567656.1	n.23+2083T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108899 AN: 151920 Hom.: 40730 Cov.: 32

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

GnomAD3 exomes AF: 0.697 AC: 88336 AN: 126718 Hom.: 31684 AF XY: 0.693 AC XY: 48107 AN XY: 69442

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 SAS exome AF: 0.732

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.: 0 AF XY: 0.666 AC XY: 114632 AN XY: 172106

Gnomad4 AFR exome AF: 0.919

Gnomad4 AMR exome AF: 0.716

Gnomad4 ASJ exome AF: 0.684

Gnomad4 EAS exome AF: 0.951

Gnomad4 SAS exome AF: 0.726

Gnomad4 FIN exome AF: 0.618

Gnomad4 NFE exome AF: 0.600

Gnomad4 OTH exome AF: 0.668

GnomAD4 genome AF: 0.717 AC: 109015 AN: 152036 Hom.: 40791 Cov.: 32 AF XY: 0.720 AC XY: 53490 AN XY: 74336

Gnomad4 AFR AF: 0.914

Gnomad4 AMR AF: 0.729

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.949

Gnomad4 SAS AF: 0.760

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.715

Alfa AF: 0.624 Hom.: 4629

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

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

Other links and lift over

dbSNP: rs7980799; hg19: chr12-33576990;