chr14-61996251-C-G

Variant names:

• chr14-61996251-C-G
• NM_001367656.1:c.232C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001367656.1(SYT16):​c.232C>G​(p.Gln78Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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: 6.8e-7 (0 hom.)
• Consequence: SYT16 NM_001367656.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0770
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050133318).

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.232C>G	p.Gln78Glu	missense	Exon 3 of 8	NP_001354585.1	Q17RD7-1
	SYT16	NM_001367661.1		c.232C>G	p.Gln78Glu	missense	Exon 4 of 9	NP_001354590.1	Q17RD7-1
	SYT16	NM_001367663.1		c.232C>G	p.Gln78Glu	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.232C>G	p.Gln78Glu	missense	Exon 3 of 8	ENSP00000508274.1	Q17RD7-1
	SYT16	ENST00000568344.5	TSL:1	c.232C>G	p.Gln78Glu	missense	Exon 1 of 6	ENSP00000478637.1	Q17RD7-1
	SYT16	ENST00000883052.1		c.232C>G	p.Gln78Glu	missense	Exon 3 of 8	ENSP00000553111.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461344 Hom.: 0 Cov.: 58 AF XY: 0.00 AC XY: 0 AN XY: 726944

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111642

Other (OTH) AF: 0.00 AC: 0 AN: 60358

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	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.95
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.077
PrimateAI	Benign	0.20	T
Sift4G	Benign	0.64	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.13		Gain of relative solvent accessibility (P = 0.0999)
MVP		0.29
ClinPred		0.052	T
GERP RS		2.3
PromoterAI		0.019	Neutral
Varity_R		0.079
gMVP		0.080
Mutation Taster		=94/6	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

hg19: chr14-62462969;