Variant 5-150648205-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_007286.6(SYNPO):c.-71C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000067 in 1,596,874 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: 𝑓 0.00027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

SYNPO
NM_007286.6 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0710

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:

SYNPO (HGNC:):

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=0.008579761).

BS2

High AC in GnomAd4 at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNPO	NM_007286.6 linkuse as main transcript	c.-71C>T		5_prime_UTR_premature_start_codon_gain_variant	2/3	ENST00000307662.5	NP_009217.3	Q8N3V7-2
SYNPO	NM_007286.6 linkuse as main transcript	c.-71C>T		5_prime_UTR_variant	2/3	ENST00000307662.5	NP_009217.3	Q8N3V7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNPO	ENST00000307662 linkuse as main transcript	c.-71C>T		5_prime_UTR_premature_start_codon_gain_variant	2/3	1	NM_007286.6	ENSP00000302139.4		Q8N3V7-2
SYNPO	ENST00000307662 linkuse as main transcript	c.-71C>T		5_prime_UTR_variant	2/3	1	NM_007286.6	ENSP00000302139.4		Q8N3V7-2

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

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:

0.000164

AC:

AN:

218866

Hom.:

AF XY:

0.000185

AC XY:

AN XY:

118818

show subpopulations

Gnomad AFR exome

AF:

0.00104

Gnomad AMR exome

AF:

0.000131

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00111

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000182

GnomAD4 exome

AF:

0.0000457

AC:

AN:

1444556

Hom.:

Cov.:

AF XY:

0.0000516

AC XY:

AN XY:

716950

show subpopulations

Gnomad4 AFR exome

AF:

0.000875

Gnomad4 AMR exome

AF:

0.000146

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000359

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000634

Gnomad4 OTH exome

AF:

0.000167

GnomAD4 genome

AF:

0.000269

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000114

Hom.:

Bravo

AF:

0.000397

ExAC

AF:

0.0000910

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

Apr 05, 2023

The c.662C>T (p.S221L) alteration is located in exon 3 (coding exon 2) of the SYNPO gene. This alteration results from a C to T substitution at nucleotide position 662, causing the serine (S) at amino acid position 221 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

0.087

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.20

T;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.55

.;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.0086

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.039

Sift

Uncertain

0.0050

D;D

Sift4G

Benign

0.065

T;T

Polyphen

0.0040

B;B

Vest4

0.054

MVP

0.082

MPC

0.31

ClinPred

0.022

GERP RS

3.0

Varity_R

0.061

gMVP

0.32

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.

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