12-33392581-T-G

Variant names:

• chr12-33392581-T-G
• rs1994169
• NM_198992.4:c.1078-7290A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198992.4(SYT10):​c.1078-7290A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,860 control chromosomes in the GnomAD database, including 18,403 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 0.47 (18403 hom., cov: 31)
• Consequence: SYT10 NM_198992.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198992.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT10	NM_198992.4	MANE Select	c.1078-7290A>C		intron	N/A	NP_945343.1	Q6XYQ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT10	ENST00000228567.7	TSL:1 MANE Select	c.1078-7290A>C		intron	N/A	ENSP00000228567.3	Q6XYQ8
	SYT10	ENST00000539102.1	TSL:1	n.*673-7290A>C		intron	N/A	ENSP00000444577.1	F5GZB8

Frequencies

GnomAD3 genomes AF: 0.468 AC: 70941 AN: 151742 Hom.: 18365 Cov.: 31

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.449

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.468 AC: 71048 AN: 151860 Hom.: 18403 Cov.: 31 AF XY: 0.471 AC XY: 34951 AN XY: 74194

African (AFR) AF: 0.650 AC: 26924 AN: 41400

American (AMR) AF: 0.460 AC: 7018 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1439 AN: 3464

East Asian (EAS) AF: 0.886 AC: 4552 AN: 5138

South Asian (SAS) AF: 0.450 AC: 2165 AN: 4808

European-Finnish (FIN) AF: 0.341 AC: 3583 AN: 10522

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23863 AN: 67964

Other (OTH) AF: 0.453 AC: 953 AN: 2104

Alfa AF: 0.415 Hom.: 5610

Bravo AF: 0.484

Asia WGS AF: 0.660 AC: 2291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1994169; hg19: chr12-33545516;