Variant 5-150618566-G-C 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.199G>C(p.Asp67His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000987 in 1,550,418 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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. D67N) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000058 ( 1 hom. )

Consequence

SYNPO
ENST00000394243.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.11

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=0.0048027635).

BS2

High AC in GnomAd4 at 72 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein
SYNPO	NM_001166208.2 linkuse as main transcript	c.199G>C	p.Asp67His	missense_variant	2/3	NP_001159680.1
SYNPO	NM_001166209.2 linkuse as main transcript	c.199G>C	p.Asp67His	missense_variant	2/3	NP_001159681.1
SYNPO	XM_006714755.4 linkuse as main transcript	c.199G>C	p.Asp67His	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.199G>C	p.Asp67His	missense_variant	2/3	1		ENSP00000377789	A2	Q8N3V7-1
SYNPO	ENST00000522122.1 linkuse as main transcript	c.199G>C	p.Asp67His	missense_variant	2/3	2		ENSP00000428378	A2	Q8N3V7-1

Frequencies

GnomAD3 genomes

AF:

0.000473

AC:

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000130

AC:

AN:

153396

Hom.:

AF XY:

0.0000614

AC XY:

AN XY:

81414

show subpopulations

Gnomad AFR exome

AF:

0.00240

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000579

AC:

AN:

1398212

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

689424

show subpopulations

Gnomad4 AFR exome

AF:

0.00222

Gnomad4 AMR exome

AF:

0.000140

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000863

GnomAD4 genome

AF:

0.000473

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00169

Gnomad4 AMR

AF:

0.000131

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

Alfa

AF:

0.0000294

Hom.:

ExAC

AF:

0.000190

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.070

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.27

.;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.0048

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.080

N;N

REVEL

Benign

0.040

Sift

Uncertain

0.016

D;D

Sift4G

Benign

0.13

T;T

Polyphen

0.016

B;B

Vest4

0.029

MVP

0.10

MPC

0.41

ClinPred

0.035

GERP RS

3.6

Varity_R

0.062

gMVP

0.079

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over