7-106099254-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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

7
7
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.92
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]

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=0.061648488).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYPL1NM_182715.4 linkc.98G>A p.Cys33Tyr missense_variant Exon 2 of 5 ENST00000455385.7 NP_874384.1 Q16563-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYPL1ENST00000455385.7 linkc.98G>A p.Cys33Tyr missense_variant Exon 2 of 5 1 NM_182715.4 ENSP00000388336.2 Q16563-2

Frequencies

GnomAD3 genomes
AF:
0.000819
AC:
124
AN:
151432
Hom.:
1
Cov.:
33
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
GnomAD3 exomes
AF:
0.000933
AC:
234
AN:
250746
Hom.:
0
AF XY:
0.000982
AC XY:
133
AN XY:
135498
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 SAS 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.:
0
Cov.:
31
AF XY:
0.000571
AC XY:
415
AN XY:
726926
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000135
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00582
Gnomad4 NFE exome
AF:
0.000433
Gnomad4 OTH exome
AF:
0.000431
GnomAD4 genome
AF:
0.000818
AC:
124
AN:
151550
Hom.:
1
Cov.:
33
AF XY:
0.00107
AC XY:
79
AN XY:
74032
show subpopulations
Gnomad4 AFR
AF:
0.0000243
Gnomad4 AMR
AF:
0.000394
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00571
Gnomad4 NFE
AF:
0.000825
Gnomad4 OTH
AF:
0.000477
Alfa
AF:
0.000680
Hom.:
0
Bravo
AF:
0.000246
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.000741
AC:
90
EpiCase
AF:
0.000655
EpiControl
AF:
0.000237

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Intellectual disability Uncertain:1
Oct 16, 2020
Center for Statistical Genetics, Columbia University
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Uncertain
0.030
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.42
.;T;.
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Pathogenic
0.97
D;D;D
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.062
T;T;T
MetaSVM
Benign
-0.56
T
MutationAssessor
Pathogenic
3.2
.;M;.
PrimateAI
Uncertain
0.72
T
PROVEAN
Pathogenic
-7.7
D;D;D
REVEL
Uncertain
0.51
Sift
Pathogenic
0.0
D;D;D
Sift4G
Uncertain
0.0040
D;D;D
Polyphen
1.0
.;D;.
Vest4
0.89
MVP
0.38
MPC
0.72
ClinPred
0.41
T
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.92
gMVP
0.95

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

LitVar

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

Other links and lift over

dbSNP: rs141399410; hg19: chr7-105739700; API