rs148367718

Variant summary

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

The NM_001114133.3(SYNPO2L):​c.2389C>T​(p.Pro797Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. P797A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

SYNPO2L
NM_001114133.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.524
Variant links:
Genes affected
SYNPO2L (HGNC:23532): (synaptopodin 2 like) Predicted to enable actin binding activity. Predicted to be involved in several processes, including positive regulation of Rho protein signal transduction; positive regulation of stress fiber assembly; and sarcomere organization. Located in cell junction; cytosol; and nuclear speck. [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=0.029407233).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYNPO2LNM_001114133.3 linkc.2389C>T p.Pro797Ser missense_variant Exon 4 of 4 ENST00000394810.3 NP_001107605.1 Q9H987-1
SYNPO2LNM_024875.5 linkc.1717C>T p.Pro573Ser missense_variant Exon 2 of 2 NP_079151.2 Q9H987-2A0A024QZQ8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYNPO2LENST00000394810.3 linkc.2389C>T p.Pro797Ser missense_variant Exon 4 of 4 1 NM_001114133.3 ENSP00000378289.2 Q9H987-1
SYNPO2LENST00000372873.8 linkc.1717C>T p.Pro573Ser missense_variant Exon 2 of 2 1 ENSP00000361964.4 Q9H987-2

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152086
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251412
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135878
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000192
AC:
28
AN:
1461884
Hom.:
0
Cov.:
37
AF XY:
0.0000124
AC XY:
9
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.000388
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152086
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74302
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.067
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
0.19
DANN
Benign
0.81
DEOGEN2
Benign
0.0042
.;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.079
N
LIST_S2
Benign
0.51
T;T
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.029
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.53
.;N
PrimateAI
Benign
0.45
T
PROVEAN
Benign
0.45
N;N
REVEL
Benign
0.032
Sift
Benign
0.61
T;T
Sift4G
Benign
0.78
T;T
Polyphen
0.0
B;B
Vest4
0.11
MutPred
0.20
.;Gain of phosphorylation at P797 (P = 0.0191);
MVP
0.16
MPC
0.38
ClinPred
0.026
T
GERP RS
0.69
Varity_R
0.029
gMVP
0.22

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: rs148367718; hg19: chr10-75407021; COSMIC: COSV100866407; API