rs1001349400

Variant names:

• chr6-158718192-C-A
• rs1001349400
• NM_001242394.2:c.701C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-158718192-C-A
• chr6-158718192-C-T

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.701C>A​(p.Ala234Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000217 in 1,385,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. A234V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: SYTL3 NM_001242394.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.46
• 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=0.2379998).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYTL3	NM_001242394.2	c.701C>A	p.Ala234Glu	missense_variant	Exon 10 of 18	ENST00000611299.5	NP_001229323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYTL3	ENST00000611299.5	c.701C>A	p.Ala234Glu	missense_variant	Exon 10 of 18	5	NM_001242394.2	ENSP00000483936.1
SYTL3	ENST00000360448.8	c.701C>A	p.Ala234Glu	missense_variant	Exon 11 of 19	5		ENSP00000353631.4
SYTL3	ENST00000367081.7	c.517-7311C>A		intron_variant	Intron 8 of 15	5		ENSP00000356048.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000217 AC: 3 AN: 1385210 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 683176

African (AFR) AF: 0.0000322 AC: 1 AN: 31044

American (AMR) AF: 0.00 AC: 0 AN: 34490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24780

East Asian (EAS) AF: 0.00 AC: 0 AN: 34722

South Asian (SAS) AF: 0.0000258 AC: 2 AN: 77428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5632

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1072010

Other (OTH) AF: 0.00 AC: 0 AN: 57480

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0040	T;T;T
Eigen	Benign	0.13
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.67	.;T;.
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;M;M
PhyloP100		4.5
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.5	.;.;N
REVEL	Benign	0.12
Sift	Benign	0.43	.;.;T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.87	P;P;P
Vest4		0.42
MutPred		0.27		Gain of solvent accessibility (P = 0.026);Gain of solvent accessibility (P = 0.026);Gain of solvent accessibility (P = 0.026);
MVP		0.38
MPC		0.14
ClinPred		0.96	D
GERP RS		5.2
Varity_R		0.17
gMVP		0.41
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1001349400; hg19: chr6-159139224;