chr10-73647466-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001114133.3(SYNPO2L):c.2186C>T(p.Pro729Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000484 in 1,446,512 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: not found (cov: 31)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
SYNPO2L
NM_001114133.3 missense
NM_001114133.3 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 4.73
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.121525586).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SYNPO2L | NM_001114133.3 | c.2186C>T | p.Pro729Leu | missense_variant | 4/4 | ENST00000394810.3 | NP_001107605.1 | |
SYNPO2L | NM_024875.5 | c.1514C>T | p.Pro505Leu | missense_variant | 2/2 | NP_079151.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SYNPO2L | ENST00000394810.3 | c.2186C>T | p.Pro729Leu | missense_variant | 4/4 | 1 | NM_001114133.3 | ENSP00000378289 | P1 | |
SYNPO2L | ENST00000372873.8 | c.1514C>T | p.Pro505Leu | missense_variant | 2/2 | 1 | ENSP00000361964 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD3 exomes AF: 0.00000419 AC: 1AN: 238410Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 129696
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GnomAD4 exome AF: 0.00000484 AC: 7AN: 1446512Hom.: 0 Cov.: 37 AF XY: 0.00000418 AC XY: 3AN XY: 717464
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GnomAD4 genome Cov.: 31
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31
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 14, 2023 | The c.2186C>T (p.P729L) alteration is located in exon 4 (coding exon 4) of the SYNPO2L gene. This alteration results from a C to T substitution at nucleotide position 2186, causing the proline (P) at amino acid position 729 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;B
Vest4
MutPred
0.15
.;Loss of glycosylation at P729 (P = 0.0224);
MVP
MPC
1.2
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at