6-158665484-A-G

Variant names:

• chr6-158665484-A-G
• rs1359502238
• NM_001242394.2:c.200A>G

Variant summary

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

The NM_001242394.2(SYTL3):​c.200A>G​(p.Gln67Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,606,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SYTL3 NM_001242394.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.24
• Publications: 0 publications found

Genes affected

SYTL3 (HGNC:15587): (synaptotagmin like 3) The protein encoded by this gene belongs to a family of peripheral membrane proteins that play a role in vesicular trafficking. This protein binds phospholipids in the presence of calcium ions. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

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=0.1877433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYTL3	NM_001242394.2	c.200A>G	p.Gln67Arg	missense_variant	Exon 5 of 18	ENST00000611299.5	NP_001229323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYTL3	ENST00000611299.5	c.200A>G	p.Gln67Arg	missense_variant	Exon 5 of 18	5	NM_001242394.2	ENSP00000483936.1
SYTL3	ENST00000360448.8	c.200A>G	p.Gln67Arg	missense_variant	Exon 6 of 19	5		ENSP00000353631.4
SYTL3	ENST00000367081.7	c.200A>G	p.Gln67Arg	missense_variant	Exon 5 of 16	5		ENSP00000356048.4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152254 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.00000427 AC: 1 AN: 234166 AF XY: 0.00

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: 0.000174

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1454204 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722544

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 43502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25900

East Asian (EAS) AF: 0.00 AC: 0 AN: 39410

South Asian (SAS) AF: 0.00 AC: 0 AN: 84700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52680

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1108750

Other (OTH) AF: 0.0000166 AC: 1 AN: 60104

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152254 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74388

African (AFR) AF: 0.00 AC: 0 AN: 41478

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.200A>G (p.Q67R) alteration is located in exon 5 (coding exon 2) of the SYTL3 gene. This alteration results from a A to G substitution at nucleotide position 200, causing the glutamine (Q) at amino acid position 67 to be replaced by an arginine (R). 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	0.066
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	9.3
DANN	Benign	0.95
DEOGEN2	Benign	0.31	.;T;T;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.71	T;.;T;.
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.1	M;M;M;M
PhyloP100		2.2
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.6	.;D;.;D
REVEL	Benign	0.17
Sift	Benign	0.22	.;T;.;T
Sift4G	Benign	0.37	T;T;T;T
Polyphen		0.48	P;B;B;B
Vest4		0.32
MutPred		0.35		Gain of MoRF binding (P = 0.0294);Gain of MoRF binding (P = 0.0294);Gain of MoRF binding (P = 0.0294);Gain of MoRF binding (P = 0.0294);
MVP		0.53
MPC		0.018
ClinPred		0.21	T
GERP RS		0.55
Varity_R		0.15
gMVP		0.49
Mutation Taster		=255/45	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: rs1359502238; hg19: chr6-159086516;