dbSNP rs141399410: SYPL1:p.Cys33Tyr (chr7-106099254-C-T) – 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_182715.4(SYPL1):c.98G>A(p.Cys33Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000591 in 1,612,830 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00082 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00057 ( 0 hom. )

Consequence

SYPL1
NM_182715.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.92

Publications

5 publications found

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 was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.061648488).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182715.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYPL1	NM_182715.4	MANE Select	c.98G>A	p.Cys33Tyr	missense	Exon 2 of 5	NP_874384.1	Q16563-2
SYPL1	NM_001381910.1		c.230G>A	p.Cys77Tyr	missense	Exon 4 of 7	NP_001368839.1	A0A994J846
SYPL1	NM_001381911.1		c.176G>A	p.Cys59Tyr	missense	Exon 3 of 6	NP_001368840.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYPL1	ENST00000455385.7	TSL:1 MANE Select	c.98G>A	p.Cys33Tyr	missense	Exon 2 of 5	ENSP00000388336.2	Q16563-2
SYPL1	ENST00000011473.6	TSL:1	c.152G>A	p.Cys51Tyr	missense	Exon 3 of 6	ENSP00000011473.2	Q16563-1
SYPL1	ENST00000706299.1		c.230G>A	p.Cys77Tyr	missense	Exon 4 of 7	ENSP00000516340.1	A0A994J846

Frequencies

GnomAD3 genomes

AF:

0.000819

AC:

124

AN:

151432

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00571

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000825

Gnomad OTH

AF:

0.000482

GnomAD2 exomes

AF:

0.000933

AC:

234

AN:

250746

AF XY:

0.000982

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00638

Gnomad NFE exome

AF:

0.000731

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000567

AC:

829

AN:

1461280

Hom.:

Cov.:

AF XY:

0.000571

AC XY:

415

AN XY:

726926

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33442

American (AMR)

AF:

0.000135

AC:

AN:

44572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

86090

European-Finnish (FIN)

AF:

0.00582

AC:

311

AN:

53412

Middle Eastern (MID)

AF:

0.000868

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000433

AC:

481

AN:

1111852

Other (OTH)

AF:

0.000431

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

137

183

229

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000818

AC:

124

AN:

151550

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74032

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41230

American (AMR)

AF:

0.000394

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5104

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00571

AC:

AN:

10516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000825

AC:

AN:

67884

Other (OTH)

AF:

0.000477

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000698

Hom.:

Bravo

AF:

0.000246

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000741

AC:

EpiCase

AF:

0.000655

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Intellectual disability (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.42

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.89

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.034

MetaRNN

Benign

0.062

MetaSVM

Benign

-0.56

MutationAssessor

Pathogenic

3.2

PhyloP100

3.9

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-7.7

REVEL

Uncertain

0.51

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.89

MVP

0.38

MPC

0.72

ClinPred

0.41

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.92

gMVP

0.95

Mutation Taster

=76/24

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over