14-61996515-T-G

Variant names:

• chr14-61996515-T-G
• rs1299416149
• NM_001367656.1:c.496T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367656.1(SYT16):​c.496T>G​(p.Leu166Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SYT16 NM_001367656.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.432
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08629581).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367656.1. 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
	SYT16	NM_001367656.1	MANE Select	c.496T>G	p.Leu166Val	missense	Exon 3 of 8	NP_001354585.1	Q17RD7-1
	SYT16	NM_001367661.1		c.496T>G	p.Leu166Val	missense	Exon 4 of 9	NP_001354590.1	Q17RD7-1
	SYT16	NM_001367663.1		c.496T>G	p.Leu166Val	missense	Exon 3 of 8	NP_001354592.1	Q17RD7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT16	ENST00000683842.1	MANE Select	c.496T>G	p.Leu166Val	missense	Exon 3 of 8	ENSP00000508274.1	Q17RD7-1
	SYT16	ENST00000568344.5	TSL:1	c.496T>G	p.Leu166Val	missense	Exon 1 of 6	ENSP00000478637.1	Q17RD7-1
	SYT16	ENST00000883052.1		c.496T>G	p.Leu166Val	missense	Exon 3 of 8	ENSP00000553111.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000414 AC: 1 AN: 241720 AF XY: 0.00000762

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455058 Hom.: 0 Cov.: 34 AF XY: 0.00000277 AC XY: 2 AN XY: 723230

African (AFR) AF: 0.00 AC: 0 AN: 33214

American (AMR) AF: 0.00 AC: 0 AN: 43472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25848

East Asian (EAS) AF: 0.00 AC: 0 AN: 39582

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108762

Other (OTH) AF: 0.00 AC: 0 AN: 60066

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.43
PrimateAI	Benign	0.38	T
Sift4G	Benign	0.53	T
Polyphen		0.018	B
Vest4		0.10
MutPred		0.17		Gain of loop (P = 0.0435)
MVP		0.16
ClinPred		0.23	T
GERP RS		1.6
Varity_R		0.051
gMVP		0.16
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1299416149; hg19: chr14-62463233;