5-150648043-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000307662.5(SYNPO):​c.-233A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,399,530 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: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

SYNPO
ENST00000307662.5 5_prime_UTR

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.530
Variant links:
Genes affected
SYNPO (HGNC:30672): (synaptopodin) Synaptopodin is an actin-associated protein that may play a role in actin-based cell shape and motility. The name synaptopodin derives from the protein's associations with postsynaptic densities and dendritic spines and with renal podocytes (Mundel et al., 1997 [PubMed 9314539]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.055800587).
BS2
High AC in GnomAdExome4 at 25 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SYNPONM_007286.6 linkuse as main transcriptc.-233A>G 5_prime_UTR_variant 2/3 ENST00000307662.5 NP_009217.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SYNPOENST00000307662.5 linkuse as main transcriptc.-233A>G 5_prime_UTR_variant 2/31 NM_007286.6 ENSP00000302139 P2Q8N3V7-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000319
AC:
5
AN:
156880
Hom.:
0
AF XY:
0.0000481
AC XY:
4
AN XY:
83086
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000588
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:
0.00
GnomAD4 exome
AF:
0.0000179
AC:
25
AN:
1399530
Hom.:
0
Cov.:
32
AF XY:
0.0000203
AC XY:
14
AN XY:
690274
show subpopulations
Gnomad4 AFR exome
AF:
0.0000633
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000755
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000185
Gnomad4 OTH exome
AF:
0.0000345
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.000153
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.0000550
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 GeneticsDec 21, 2022The c.500A>G (p.N167S) alteration is located in exon 3 (coding exon 2) of the SYNPO gene. This alteration results from a A to G substitution at nucleotide position 500, causing the asparagine (N) at amino acid position 167 to be replaced by a serine (S). 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
0.061
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
15
DANN
Benign
0.96
DEOGEN2
Benign
0.27
T;T
Eigen
Benign
-0.42
Eigen_PC
Benign
-0.31
FATHMM_MKL
Benign
0.65
D
LIST_S2
Benign
0.71
.;T
M_CAP
Benign
0.0044
T
MetaRNN
Benign
0.056
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.3
L;L
MutationTaster
Benign
1.0
D;D;N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-2.3
N;N
REVEL
Benign
0.019
Sift
Benign
0.37
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0030
B;B
Vest4
0.29
MutPred
0.22
Gain of phosphorylation at N167 (P = 0.0203);Gain of phosphorylation at N167 (P = 0.0203);
MVP
0.47
MPC
0.29
ClinPred
0.038
T
GERP RS
1.5
Varity_R
0.050
gMVP
0.10

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: rs751195238; hg19: chr5-150027605; API