chr12-33379909-C-T

Position:

• chr12-33379909-C-T

Variant summary

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

The NM_198992.4(SYT10):​c.1423G>A​(p.Gly475Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYT10 NM_198992.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.89

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/exons	MANE	UniProt
SYT10	NM_198992.4	c.1423G>A	p.Gly475Ser	missense_variant	6/7	ENST00000228567.7
SYT10	XM_011520644.4	c.880G>A	p.Gly294Ser	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYT10	ENST00000228567.7	c.1423G>A	p.Gly475Ser	missense_variant	6/7	1	NM_198992.4	P1
SYT10	ENST00000539102.1	c.*1018G>A		3_prime_UTR_variant, NMD_transcript_variant	8/9	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2022

The c.1423G>A (p.G475S) alteration is located in exon 6 (coding exon 6) of the SYT10 gene. This alteration results from a G to A substitution at nucleotide position 1423, causing the glycine (G) at amino acid position 475 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	D
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.31
Sift	Benign	0.12	T
Sift4G	Benign	0.14	T
Polyphen		0.35	B
Vest4		0.53
MutPred		0.45		Gain of catalytic residue at R478 (P = 0.0026);
MVP		0.78
MPC		0.41
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.27
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-33532844; COSMIC: COSV57337432;