Genetic Variant SYT16:p.Met120Val (chr14-61996377-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001367656.1(SYT16):c.358A>G(p.Met120Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,460 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 1 hom. )

Consequence

SYT16
NM_001367656.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.312

Variant links:

Genes affected

SYT16 (HGNC:23142): (synaptotagmin 16) Predicted to enable identical protein binding activity and phospholipid binding activity. Predicted to be involved in exocytosis. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SYT16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.035707384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT16	NM_001367656.1 link	c.358A>G	p.Met120Val	missense_variant	Exon 3 of 8	ENST00000683842.1	NP_001354585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYT16	ENST00000683842.1 link	c.358A>G	p.Met120Val	missense_variant	Exon 3 of 8		NM_001367656.1	ENSP00000508274.1	Q17RD7-1
SYT16	ENST00000568344.5 link	c.358A>G	p.Met120Val	missense_variant	Exon 1 of 6	1		ENSP00000478637.1	Q17RD7-1
SYT16	ENST00000636133.1 link	c.193+26066A>G		intron_variant	Intron 2 of 3	5		ENSP00000490266.1	A0A1B0GUW0
SYT16	ENST00000555409.1 link	n.358A>G		non_coding_transcript_exon_variant	Exon 1 of 7	5		ENSP00000451035.1	Q17RD7-4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000242

AC:

AN:

248168

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134576

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.00000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461278

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726906

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000262

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.358A>G (p.M120V) alteration is located in exon 1 (coding exon 1) of the SYT16 gene. This alteration results from a A to G substitution at nucleotide position 358, causing the methionine (M) at amino acid position 120 to be replaced by a valine (V). 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

0.057

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.12

DANN

Benign

0.56

DEOGEN2

Benign

0.0037

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.51

M_CAP

Benign

0.0014

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.92

PrimateAI

Benign

0.23

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.015

MutPred

0.092

Loss of phosphorylation at S116 (P = 0.2077);

MVP

0.11

ClinPred

0.073

GERP RS

2.1

Varity_R

0.051

gMVP

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over