NM_001367656.1:c.47C>A

Variant names:

• chr14-61996066-C-A
• rs1409503101
• NM_001367656.1:c.47C>A

Variant summary

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

The NM_001367656.1(SYT16):​c.47C>A​(p.Pro16His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,166 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P16L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SYT16 NM_001367656.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.30
• 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 2 ACMG points.

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

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.47C>A	p.Pro16His	missense	Exon 3 of 8	NP_001354585.1	Q17RD7-1
	SYT16	NM_001367661.1		c.47C>A	p.Pro16His	missense	Exon 4 of 9	NP_001354590.1	Q17RD7-1
	SYT16	NM_001367663.1		c.47C>A	p.Pro16His	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.47C>A	p.Pro16His	missense	Exon 3 of 8	ENSP00000508274.1	Q17RD7-1
	SYT16	ENST00000568344.5	TSL:1	c.47C>A	p.Pro16His	missense	Exon 1 of 6	ENSP00000478637.1	Q17RD7-1
	SYT16	ENST00000883052.1		c.47C>A	p.Pro16His	missense	Exon 3 of 8	ENSP00000553111.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458166 Hom.: 0 Cov.: 58 AF XY: 0.00000138 AC XY: 1 AN XY: 725040

African (AFR) AF: 0.00 AC: 0 AN: 33296

American (AMR) AF: 0.00 AC: 0 AN: 44292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25984

East Asian (EAS) AF: 0.00 AC: 0 AN: 39610

South Asian (SAS) AF: 0.00 AC: 0 AN: 85716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110018

Other (OTH) AF: 0.00 AC: 0 AN: 60206

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.3
PrimateAI	Uncertain	0.59	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.63
MutPred		0.59		Gain of helix (P = 0.0225)
MVP		0.68
ClinPred		0.93	D
GERP RS		5.0
PromoterAI		0.00010	Neutral
Varity_R		0.31
gMVP		0.42
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs1409503101; hg19: chr14-62462784;