6-158745498-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001242394.2(SYTL3):c.874G>A(p.Asp292Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SYTL3 NM_001242394.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.28

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062054783).
• BP6: Variant 6-158745498-G-A is Benign according to our data. Variant chr6-158745498-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2546101.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYTL3	NM_001242394.2	c.874G>A	p.Asp292Asn	missense_variant	12/18	ENST00000611299.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYTL3	ENST00000611299.5	c.874G>A	p.Asp292Asn	missense_variant	12/18	5	NM_001242394.2	P1
SYTL3	ENST00000360448.8	c.874G>A	p.Asp292Asn	missense_variant	13/19	5		P1
SYTL3	ENST00000367081.7	c.670G>A	p.Asp224Asn	missense_variant	10/16	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457882 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725126

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000229

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
Cadd	Benign	16
Dann	Benign	0.63
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.58	T;.;T;.
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.062	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.33	T
REVEL	Benign	0.10
Sift4G	Benign	0.34	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.24
MutPred		0.38		.;Loss of phosphorylation at S287 (P = 0.1234);Loss of phosphorylation at S287 (P = 0.1234);Loss of phosphorylation at S287 (P = 0.1234);
MVP		0.17
MPC		0.017
ClinPred		0.11	T
GERP RS		4.3
Varity_R		0.044
gMVP		0.20

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: chr6-159166530;