Genetic Variant ENST00000394243.5:c.-265-129T>C (chr5-150617974-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000394243.5(SYNPO):c.-265-129T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 167,402 control chromosomes in the GnomAD database, including 2,099 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 2010 hom., cov: 32)

Exomes 𝑓: 0.050 ( 89 hom. )

Consequence

SYNPO
ENST00000394243.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.527

Publications

1 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 Gene-Disease associations (from GenCC):

focal segmental glomerulosclerosis
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

SYNPO links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 5-150617974-T-C is Benign according to our data. Variant chr5-150617974-T-C is described in ClinVar as Benign. ClinVar VariationId is 1226601.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000394243.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNPO	NM_001166208.2		c.-265-129T>C		intron	N/A	NP_001159680.1	Q8N3V7-1
	SYNPO	NM_001166209.2		c.-265-129T>C		intron	N/A	NP_001159681.1	Q8N3V7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNPO	ENST00000394243.5	TSL:1	c.-265-129T>C		intron	N/A	ENSP00000377789.1	Q8N3V7-1
	SYNPO	ENST00000522122.1	TSL:2	c.-265-129T>C		intron	N/A	ENSP00000428378.1	Q8N3V7-1

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15977

AN:

152060

Hom.:

2001

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0392

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.0273

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0134

Gnomad OTH

AF:

0.0642

GnomAD4 exome

AF:

0.0504

AC:

767

AN:

15224

Hom.:

AF XY:

0.0451

AC XY:

345

AN XY:

7654

show subpopulations

African (AFR)

AF:

0.288

AC:

184

AN:

638

American (AMR)

AF:

0.0392

AC:

AN:

586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

658

East Asian (EAS)

AF:

0.292

AC:

293

AN:

1002

South Asian (SAS)

AF:

0.156

AC:

AN:

218

European-Finnish (FIN)

AF:

0.0410

AC:

AN:

536

Middle Eastern (MID)

AF:

0.0263

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0143

AC:

151

AN:

10564

Other (OTH)

AF:

0.0613

AC:

AN:

946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

114

142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.105

AC:

16017

AN:

152178

Hom.:

2010

Cov.:

AF XY:

0.107

AC XY:

7970

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.286

AC:

11853

AN:

41468

American (AMR)

AF:

0.0392

AC:

599

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.269

AC:

1391

AN:

5176

South Asian (SAS)

AF:

0.171

AC:

825

AN:

4822

European-Finnish (FIN)

AF:

0.0273

AC:

290

AN:

10610

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0134

AC:

911

AN:

68020

Other (OTH)

AF:

0.0659

AC:

139

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

630

1261

1891

2522

3152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

170

340

510

680

850

<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:

0.0650

Hom.:

143

Bravo

AF:

0.113

Asia WGS

AF:

0.231

AC:

800

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.5

(source)

DANN

Benign

0.76

PhyloP100

0.53

PromoterAI

-0.011

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over