chr10-73647466-G-A

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

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.73
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]

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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
SYNPO2LNM_001114133.3 linkuse as main transcriptc.2186C>T p.Pro729Leu missense_variant 4/4 ENST00000394810.3 NP_001107605.1
SYNPO2LNM_024875.5 linkuse as main transcriptc.1514C>T p.Pro505Leu missense_variant 2/2 NP_079151.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SYNPO2LENST00000394810.3 linkuse as main transcriptc.2186C>T p.Pro729Leu missense_variant 4/41 NM_001114133.3 ENSP00000378289 P1Q9H987-1
SYNPO2LENST00000372873.8 linkuse as main transcriptc.1514C>T p.Pro505Leu missense_variant 2/21 ENSP00000361964 Q9H987-2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000419
AC:
1
AN:
238410
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
129696
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000552
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000484
AC:
7
AN:
1446512
Hom.:
0
Cov.:
37
AF XY:
0.00000418
AC XY:
3
AN XY:
717464
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000454
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsAug 14, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.42
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
.;T
Eigen
Benign
0.15
Eigen_PC
Benign
0.19
FATHMM_MKL
Benign
0.72
D
LIST_S2
Benign
0.83
T;T
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.7
.;M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-3.8
D;D
REVEL
Benign
0.12
Sift
Uncertain
0.0050
D;D
Sift4G
Uncertain
0.0040
D;D
Polyphen
0.68
P;B
Vest4
0.30
MutPred
0.15
.;Loss of glycosylation at P729 (P = 0.0224);
MVP
0.59
MPC
1.2
ClinPred
0.97
D
GERP RS
4.8
Varity_R
0.32
gMVP
0.57

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: rs748283757; hg19: chr10-75407224; API