NM_001242394.2:c.191C>A

Variant names:

• chr6-158665475-C-A
• rs140236569
• NM_001242394.2:c.191C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001242394.2(SYTL3):​c.191C>A​(p.Ala64Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. A64V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYTL3 NM_001242394.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.29
• Publications: 2 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.915

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYTL3	NM_001242394.2	c.191C>A	p.Ala64Glu	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.191C>A	p.Ala64Glu	missense_variant	Exon 5 of 18	5	NM_001242394.2	ENSP00000483936.1
SYTL3	ENST00000360448.8	c.191C>A	p.Ala64Glu	missense_variant	Exon 6 of 19	5		ENSP00000353631.4
SYTL3	ENST00000367081.7	c.191C>A	p.Ala64Glu	missense_variant	Exon 5 of 16	5		ENSP00000356048.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 235904 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: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	.;D;D;D
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T;.;T;.
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.92	D;D;D;D
MetaSVM	Uncertain	0.33	D
MutationAssessor	Uncertain	2.9	M;M;M;M
PhyloP100		7.3
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.2	.;D;.;D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0020	.;D;.;D
Sift4G	Uncertain	0.0050	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.92
MutPred		0.56		Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);
MVP		0.72
MPC		0.14
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.79
gMVP		0.67
Mutation Taster		=35/65	disease causing

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: rs140236569; hg19: chr6-159086507;