Variant 10-73647531-A-AG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001114133.3(SYNPO2L):c.2120dupC(p.Pro708fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000888 in 1,580,338 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00090 ( 2 hom. )

Consequence

SYNPO2L
NM_001114133.3 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.23

Variant links:

Genes affected

SYNPO2L (HGNC:23532): (synaptopodin 2 like) Predicted to enable actin binding activity. Predicted to be involved in several processes, including positive regulation of Rho protein signal transduction; positive regulation of stress fiber assembly; and sarcomere organization. Located in cell junction; cytosol; and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

SYNPO2L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNPO2L	NM_001114133.3 linkuse as main transcript	c.2120dupC	p.Pro708fs	frameshift_variant	4/4	ENST00000394810.3	NP_001107605.1	Q9H987-1
SYNPO2L	NM_024875.5 linkuse as main transcript	c.1448dupC	p.Pro484fs	frameshift_variant	2/2		NP_079151.2	Q9H987-2A0A024QZQ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNPO2L	ENST00000394810.3 linkuse as main transcript	c.2120dupC	p.Pro708fs	frameshift_variant	4/4	1	NM_001114133.3	ENSP00000378289.2		Q9H987-1
SYNPO2L	ENST00000372873.8 linkuse as main transcript	c.1448dupC	p.Pro484fs	frameshift_variant	2/2	1		ENSP00000361964.4		Q9H987-2

Frequencies

GnomAD3 genomes

AF:

0.000722

AC:

105

AN:

145460

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000610

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000273

Gnomad ASJ

AF:

0.00296

Gnomad EAS

AF:

0.00204

Gnomad SAS

AF:

0.00132

Gnomad FIN

AF:

0.000200

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000718

Gnomad OTH

AF:

0.000999

GnomAD3 exomes

AF:

0.00101

AC:

238

AN:

236560

Hom.:

AF XY:

0.00106

AC XY:

136

AN XY:

127922

show subpopulations

Gnomad AFR exome

AF:

0.000383

Gnomad AMR exome

AF:

0.000862

Gnomad ASJ exome

AF:

0.00151

Gnomad EAS exome

AF:

0.00283

Gnomad SAS exome

AF:

0.00103

Gnomad FIN exome

AF:

0.000193

Gnomad NFE exome

AF:

0.000968

Gnomad OTH exome

AF:

0.000532

GnomAD4 exome

AF:

0.000904

AC:

1297

AN:

1434772

Hom.:

Cov.:

AF XY:

0.000942

AC XY:

669

AN XY:

710488

show subpopulations

Gnomad4 AFR exome

AF:

0.000550

Gnomad4 AMR exome

AF:

0.000891

Gnomad4 ASJ exome

AF:

0.00166

Gnomad4 EAS exome

AF:

0.00197

Gnomad4 SAS exome

AF:

0.00103

Gnomad4 FIN exome

AF:

0.000190

Gnomad4 NFE exome

AF:

0.000889

Gnomad4 OTH exome

AF:

0.000831

GnomAD4 genome

AF:

0.000728

AC:

106

AN:

145566

Hom.:

Cov.:

AF XY:

0.000633

AC XY:

AN XY:

71072

show subpopulations

Gnomad4 AFR

AF:

0.000633

Gnomad4 AMR

AF:

0.000273

Gnomad4 ASJ

AF:

0.00296

Gnomad4 EAS

AF:

0.00205

Gnomad4 SAS

AF:

0.00132

Gnomad4 FIN

AF:

0.000200

Gnomad4 NFE

AF:

0.000718

Gnomad4 OTH

AF:

0.000990

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Mar 30, 2021

SYNPO2L NM_001114133.2 exon 4 p.Pro708Serfs*13 (c.2120dup): This variant has not been reported in the literature and is not present in large control databases. Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is a duplication of 1 cytosine nucleotide in a string of 7 cytosines and is predicted to create a premature stop codon 13 amino acids downstream from this location which results in an absent or abnormal protein. However, there is insufficient evidence to establish loss of function (LOF) as a known mechanism of disease. In addition, this variant occurs within the last exon of this gene; due to its position, it is possible that this protein may escape nonsense mediated decay. Further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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