rs146345840

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_007286.6(SYNPO):c.814C>T(p.Pro272Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00661 in 1,613,852 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0068 ( 51 hom. )

Consequence

SYNPO
NM_007286.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.917

Publications

11 publications found

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 was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043495297).

BP6

Variant 5-150649089-C-T is Benign according to our data. Variant chr5-150649089-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 774 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNPO	NM_007286.6 link	c.814C>T	p.Pro272Ser	missense_variant	Exon 2 of 3	ENST00000307662.5	NP_009217.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNPO	ENST00000307662.5 link	c.814C>T	p.Pro272Ser	missense_variant	Exon 2 of 3	1	NM_007286.6	ENSP00000302139.4

Frequencies

GnomAD3 genomes

AF:

0.00509

AC:

774

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0124

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00789

Gnomad OTH

AF:

0.00526

GnomAD2 exomes

AF:

0.00485

AC:

1211

AN:

249610

AF XY:

0.00466

show subpopulations

Gnomad AFR exome

AF:

0.00120

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0105

Gnomad NFE exome

AF:

0.00783

Gnomad OTH exome

AF:

0.00558

GnomAD4 exome

AF:

0.00677

AC:

9895

AN:

1461562

Hom.:

Cov.:

AF XY:

0.00653

AC XY:

4749

AN XY:

727042

show subpopulations

African (AFR)

AF:

0.000986

AC:

AN:

33462

American (AMR)

AF:

0.00145

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.000128

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00940

AC:

502

AN:

53396

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00806

AC:

8961

AN:

1111800

Other (OTH)

AF:

0.00520

AC:

314

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

727

1454

2182

2909

3636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

330

660

990

1320

1650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00508

AC:

774

AN:

152290

Hom.:

Cov.:

AF XY:

0.00540

AC XY:

402

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00142

AC:

AN:

41558

American (AMR)

AF:

0.00216

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0124

AC:

132

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00789

AC:

537

AN:

68024

Other (OTH)

AF:

0.00520

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

124

165

206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00615

Hom.:

Bravo

AF:

0.00431

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00663

AC:

ExAC

AF:

0.00474

AC:

576

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00654

EpiControl

AF:

0.00806

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SYNPO: BP4, BS2 -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 15, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.18

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.20

T;T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.70

.;T;T;T

MetaRNN

Benign

0.0043

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L;.;.

PhyloP100

-0.92

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.8

N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.088

T;T;T;T

Sift4G

Benign

0.27

T;T;T;T

Polyphen

0.0090

B;B;B;.

Vest4

0.080

MVP

0.30

MPC

0.36

ClinPred

0.0054

GERP RS

-1.7

Varity_R

0.033

gMVP

0.31

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over