chr12-33376888-G-A

Variant names:

• chr12-33376888-G-A
• rs34361405
• NM_198992.4:c.1514C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_198992.4(SYT10):​c.1514C>T​(p.Ala505Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000656 in 1,613,998 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A505E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0032 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (3 hom.)
• Consequence: SYT10 NM_198992.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 9.19
• Publications: 9 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0072674453).
• BP6: Variant 12-33376888-G-A is Benign according to our data. Variant chr12-33376888-G-A is described in ClinVar as Benign. ClinVar VariationId is 787922.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.1514C>T	p.Ala505Val	missense	Exon 7 of 7	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.1514C>T	p.Ala505Val	missense	Exon 7 of 7	ENSP00000228567.3	Q6XYQ8
	SYT10	ENST00000539102.1	TSL:1	n.*1109C>T		non_coding_transcript_exon	Exon 9 of 9	ENSP00000444577.1	F5GZB8
	SYT10	ENST00000539102.1	TSL:1	n.*1109C>T		3_prime_UTR	Exon 9 of 9	ENSP00000444577.1	F5GZB8

Frequencies

GnomAD3 genomes AF: 0.00320 AC: 487 AN: 152104 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00973

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00446

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000840 AC: 211 AN: 251176 AF XY: 0.000604

Gnomad AFR exome AF: 0.0103

Gnomad AMR exome AF: 0.000752

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000391 AC: 571 AN: 1461776 Hom.: 3 Cov.: 30 AF XY: 0.000351 AC XY: 255 AN XY: 727192

African (AFR) AF: 0.0116 AC: 388 AN: 33474

American (AMR) AF: 0.000827 AC: 37 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5764

European-Non Finnish (NFE) AF: 0.0000809 AC: 90 AN: 1111944

Other (OTH) AF: 0.000729 AC: 44 AN: 60388

GnomAD4 genome AF: 0.00321 AC: 488 AN: 152222 Hom.: 4 Cov.: 32 AF XY: 0.00314 AC XY: 234 AN XY: 74440

African (AFR) AF: 0.00973 AC: 404 AN: 41536

American (AMR) AF: 0.00445 AC: 68 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68024

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000964 Hom.: 1

Bravo AF: 0.00375

ESP6500AA AF: 0.00726 AC: 32

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000972 AC: 118

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0073	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		9.2
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.13
Sift	Benign	0.077	T
Sift4G	Benign	0.40	T
Polyphen		0.44	B
Vest4		0.51
MVP		0.56
MPC		0.20
ClinPred		0.022	T
GERP RS		4.8
Varity_R		0.091
gMVP		0.37
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs34361405; hg19: chr12-33529823; COSMIC: COSV57338788;