Variant 5-150618484-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000394243.5(SYNPO):c.117G>T(p.Glu39Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000973 in 1,551,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

SYNPO
ENST00000394243.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.16

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]

SYNPO links:

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=0.067691505).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein
SYNPO	NM_001166208.2 linkuse as main transcript	c.117G>T	p.Glu39Asp	missense_variant	2/3	NP_001159680.1
SYNPO	NM_001166209.2 linkuse as main transcript	c.117G>T	p.Glu39Asp	missense_variant	2/3	NP_001159681.1
SYNPO	XM_006714755.4 linkuse as main transcript	c.117G>T	p.Glu39Asp	missense_variant	2/4	XP_006714818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNPO	ENST00000394243.5 linkuse as main transcript	c.117G>T	p.Glu39Asp	missense_variant	2/3	1		ENSP00000377789	A2	Q8N3V7-1
SYNPO	ENST00000522122.1 linkuse as main transcript	c.117G>T	p.Glu39Asp	missense_variant	2/3	2		ENSP00000428378	A2	Q8N3V7-1

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000585

AC:

AN:

153724

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

81604

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000406

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000653

Gnomad NFE exome

AF:

0.000118

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000104

AC:

146

AN:

1399224

Hom.:

Cov.:

AF XY:

0.000104

AC XY:

AN XY:

690100

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000203

Gnomad4 NFE exome

AF:

0.000120

Gnomad4 OTH exome

AF:

0.000259

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000173

Hom.:

Bravo

AF:

0.0000491

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.0000969

AC:

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

Sep 01, 2021

The c.117G>T (p.E39D) alteration is located in exon 2 (coding exon 1) of the SYNPO gene. This alteration results from a G to T substitution at nucleotide position 117, causing the glutamic acid (E) at amino acid position 39 to be replaced by an aspartic acid (D). 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

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.53

.;T

M_CAP

Benign

0.0092

MetaRNN

Benign

0.068

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M

MutationTaster

Benign

0.94

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.88

N;N

REVEL

Benign

0.018

Sift

Uncertain

0.020

D;D

Sift4G

Benign

0.38

T;T

Polyphen

0.033

B;B

Vest4

0.093

MutPred

0.15

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.48

MPC

0.33

ClinPred

0.16

GERP RS

3.1

Varity_R

0.22

gMVP

0.12

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over