rs200421519

Variant names:

• chr12-33376853-G-A
• rs200421519
• NM_198992.4:c.1549C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-33376853-G-A
• chr12-33376853-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198992.4(SYT10):​c.1549C>T​(p.Pro517Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYT10 NM_198992.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.19

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT10	NM_198992.4	c.1549C>T	p.Pro517Ser	missense_variant	Exon 7 of 7	ENST00000228567.7	NP_945343.1
SYT10	XM_011520644.4	c.1006C>T	p.Pro336Ser	missense_variant	Exon 6 of 6		XP_011518946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT10	ENST00000228567.7	c.1549C>T	p.Pro517Ser	missense_variant	Exon 7 of 7	1	NM_198992.4	ENSP00000228567.3
SYT10	ENST00000539102.1	n.*1144C>T		non_coding_transcript_exon_variant	Exon 9 of 9	1		ENSP00000444577.1
SYT10	ENST00000539102.1	n.*1144C>T		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000444577.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.15
Sift	Benign	0.35	T
Sift4G	Benign	0.36	T
Polyphen		0.38	B
Vest4		0.65
MutPred		0.30		Gain of catalytic residue at P519 (P = 0.001);
MVP		0.57
MPC		0.65
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.12
gMVP		0.53

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

LitVar

Other links and lift over

dbSNP: rs200421519; hg19: chr12-33529788;