14-61996314-C-G

Variant names:

• chr14-61996314-C-G
• NM_001367656.1:c.295C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001367656.1(SYT16):​c.295C>G​(p.Gln99Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/18 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)
• Consequence: SYT16 NM_001367656.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.428

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

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=0.052106023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT16	NM_001367656.1	c.295C>G	p.Gln99Glu	missense_variant	Exon 3 of 8	ENST00000683842.1	NP_001354585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT16	ENST00000683842.1	c.295C>G	p.Gln99Glu	missense_variant	Exon 3 of 8		NM_001367656.1	ENSP00000508274.1
SYT16	ENST00000568344.5	c.295C>G	p.Gln99Glu	missense_variant	Exon 1 of 6	1		ENSP00000478637.1
SYT16	ENST00000636133.1	c.193+26003C>G		intron_variant	Intron 2 of 3	5		ENSP00000490266.1
SYT16	ENST00000555409.1	n.295C>G		non_coding_transcript_exon_variant	Exon 1 of 7	5		ENSP00000451035.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.295C>G (p.Q99E) alteration is located in exon 1 (coding exon 1) of the SYT16 gene. This alteration results from a C to G substitution at nucleotide position 295, causing the glutamine (Q) at amino acid position 99 to be replaced by a glutamic acid (E). 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	0.068
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.089
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.28	T
Sift4G	Benign	0.38	T
Polyphen		0.010	B
Vest4		0.14
MutPred		0.10		Loss of loop (P = 0.0288);
MVP		0.36
ClinPred		0.21	T
GERP RS		3.5
Varity_R		0.086
gMVP		0.058

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-62463032;