12-33424055-A-C

Variant names:

• chr12-33424055-A-C
• rs7980799
• NM_198992.4:c.509+2083T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 publications found

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

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	c.509+2083T>G		intron_variant	Intron 2 of 6	ENST00000228567.7	NP_945343.1

Ensembl

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

GnomAD2 exomes AF: 0.697 AC: 88336 AN: 126718 AF XY: 0.693

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

African (AFR) AF: 0.919 AC: 7835 AN: 8530

American (AMR) AF: 0.716 AC: 19342 AN: 27010

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 7323 AN: 10704

East Asian (EAS) AF: 0.951 AC: 8735 AN: 9188

South Asian (SAS) AF: 0.726 AC: 43168 AN: 59424

European-Finnish (FIN) AF: 0.618 AC: 7610 AN: 12312

Middle Eastern (MID) AF: 0.632 AC: 1747 AN: 2764

European-Non Finnish (NFE) AF: 0.600 AC: 94846 AN: 158092

Other (OTH) AF: 0.668 AC: 9424 AN: 14116

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

African (AFR) AF: 0.914 AC: 37935 AN: 41506

American (AMR) AF: 0.729 AC: 11132 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2393 AN: 3470

East Asian (EAS) AF: 0.949 AC: 4915 AN: 5178

South Asian (SAS) AF: 0.760 AC: 3661 AN: 4816

European-Finnish (FIN) AF: 0.579 AC: 6121 AN: 10566

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40485 AN: 67924

Other (OTH) AF: 0.715 AC: 1508 AN: 2110

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
PhyloP100		-0.16
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

Other links and lift over

dbSNP: rs7980799; hg19: chr12-33576990;