Genetic Variant SYTL3:p.His212Arg (chr6-158718126-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001242394.2(SYTL3):c.635A>G(p.His212Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000323 in 1,546,622 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 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

SYTL3
NM_001242394.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

Publications

0 publications found

Variant links:

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]

SYTL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03279999).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYTL3	NM_001242394.2 link	c.635A>G	p.His212Arg	missense_variant	Exon 10 of 18	ENST00000611299.5	NP_001229323.1	Q4VX76-1B4E2A9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYTL3	ENST00000611299.5 link	c.635A>G	p.His212Arg	missense_variant	Exon 10 of 18	5	NM_001242394.2	ENSP00000483936.1	Q4VX76-1
SYTL3	ENST00000360448.8 link	c.635A>G	p.His212Arg	missense_variant	Exon 11 of 19	5		ENSP00000353631.4	Q4VX76-1
SYTL3	ENST00000367081.7 link	c.517-7377A>G		intron_variant	Intron 8 of 15	5		ENSP00000356048.4	Q4VX76-2

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000103

AC:

AN:

145570

AF XY:

0.000115

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000383

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000969

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000239

GnomAD4 exome

AF:

0.0000287

AC:

AN:

1394492

Hom.:

Cov.:

AF XY:

0.0000320

AC XY:

AN XY:

687766

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31394

American (AMR)

AF:

0.000283

AC:

AN:

35288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25074

East Asian (EAS)

AF:

0.00

AC:

AN:

35346

South Asian (SAS)

AF:

0.000203

AC:

AN:

78634

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48088

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.00000928

AC:

AN:

1077150

Other (OTH)

AF:

0.0000519

AC:

AN:

57840

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41432

American (AMR)

AF:

0.000655

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000421

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 21, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.635A>G (p.H212R) alteration is located in exon 10 (coding exon 7) of the SYTL3 gene. This alteration results from a A to G substitution at nucleotide position 635, causing the histidine (H) at amino acid position 212 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

0.080

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.64

CADD

Benign

7.9

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.0063

T;T;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.41

.;T;.

M_CAP

Benign

0.0032

MetaRNN

Benign

0.033

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.1

M;M;M

PhyloP100

1.4

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.3

.;.;N

REVEL

Benign

0.053

Sift

Benign

0.52

.;.;T

Sift4G

Benign

0.54

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.062

MutPred

0.28

Gain of MoRF binding (P = 0.0089);Gain of MoRF binding (P = 0.0089);Gain of MoRF binding (P = 0.0089);

MVP

0.067

MPC

0.017

ClinPred

0.018

GERP RS

1.4

Varity_R

0.054

gMVP

0.27

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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6-158718126-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over