Genetic Variant SYPL1:p.Glu13Lys (chr7-106112172-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_182715.4(SYPL1):c.37G>A(p.Glu13Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000816 in 1,545,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00082 ( 0 hom. )

Consequence

SYPL1
NM_182715.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20

Variant links:

Genes affected

SYPL1 (HGNC:11507): (synaptophysin like 1) Predicted to be involved in chemical synaptic transmission. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

SYPL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0646013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYPL1	NM_182715.4 link	c.37G>A	p.Glu13Lys	missense_variant	Exon 1 of 5	ENST00000455385.7	NP_874384.1	Q16563-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYPL1	ENST00000455385.7 link	c.37G>A	p.Glu13Lys	missense_variant	Exon 1 of 5	1	NM_182715.4	ENSP00000388336.2		Q16563-2

Frequencies

GnomAD3 genomes

AF:

0.000806

AC:

122

AN:

151428

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000526

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00126

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00143

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000866

AC:

199

AN:

229816

Hom.:

AF XY:

0.000806

AC XY:

101

AN XY:

125302

show subpopulations

Gnomad AFR exome

AF:

0.0000741

Gnomad AMR exome

AF:

0.000418

Gnomad ASJ exome

AF:

0.000210

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000887

Gnomad NFE exome

AF:

0.00149

Gnomad OTH exome

AF:

0.00129

GnomAD4 exome

AF:

0.000817

AC:

1138

AN:

1393472

Hom.:

Cov.:

AF XY:

0.000843

AC XY:

585

AN XY:

694050

show subpopulations

Gnomad4 AFR exome

AF:

0.0000665

Gnomad4 AMR exome

AF:

0.000416

Gnomad4 ASJ exome

AF:

0.000211

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00109

Gnomad4 NFE exome

AF:

0.000959

Gnomad4 OTH exome

AF:

0.000553

GnomAD4 genome

AF:

0.000805

AC:

122

AN:

151536

Hom.:

Cov.:

AF XY:

0.000837

AC XY:

AN XY:

74076

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.000525

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00126

Gnomad4 NFE

AF:

0.00143

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000995

Hom.:

Bravo

AF:

0.000612

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000876

AC:

106

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.91G>A (p.E31K) alteration is located in exon 2 (coding exon 2) of the SYPL1 gene. This alteration results from a G to A substitution at nucleotide position 91, causing the glutamic acid (E) at amino acid position 31 to be replaced by a lysine (K). 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

Pathogenic

0.88

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

.;T;.

Eigen

Benign

0.072

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.065

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

.;M;.

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Benign

0.13

Sift

Benign

0.032

D;D;T

Sift4G

Benign

0.11

T;T;T

Polyphen

0.16

.;B;.

Vest4

0.62

MVP

0.088

MPC

0.15

ClinPred

0.20

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.78

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over