Genetic Variant SYNPO2L:p.Pro708SerfsTer13 (chr10-73647531-A-AG) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001114133.3(SYNPO2L):c.2120dupC(p.Pro708SerfsTer13) 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

Publications

0 publications found

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:

SYNPO2L-AS1 (HGNC:55242): (SYNPO2L antisense RNA 1)

SYNPO2L-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114133.3. 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
	SYNPO2L	NM_001114133.3	MANE Select	c.2120dupC	p.Pro708SerfsTer13	frameshift	Exon 4 of 4	NP_001107605.1	Q9H987-1
	SYNPO2L	NM_024875.5		c.1448dupC	p.Pro484SerfsTer13	frameshift	Exon 2 of 2	NP_079151.2	Q9H987-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYNPO2L	ENST00000394810.3	TSL:1 MANE Select	c.2120dupC	p.Pro708SerfsTer13	frameshift	Exon 4 of 4	ENSP00000378289.2	Q9H987-1
SYNPO2L	ENST00000372873.8	TSL:1	c.1448dupC	p.Pro484SerfsTer13	frameshift	Exon 2 of 2	ENSP00000361964.4	Q9H987-2
SYNPO2L-AS1	ENST00000759288.1		n.10dupG		non_coding_transcript_exon	Exon 1 of 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

GnomAD2 exomes

AF:

0.00101

AC:

238

AN:

236560

AF XY:

0.00106

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 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

African (AFR)

AF:

0.000550

AC:

AN:

32712

American (AMR)

AF:

0.000891

AC:

AN:

42632

Ashkenazi Jewish (ASJ)

AF:

0.00166

AC:

AN:

24750

East Asian (EAS)

AF:

0.00197

AC:

AN:

39154

South Asian (SAS)

AF:

0.00103

AC:

AN:

83694

European-Finnish (FIN)

AF:

0.000190

AC:

AN:

52524

Middle Eastern (MID)

AF:

0.000889

AC:

AN:

5624

European-Non Finnish (NFE)

AF:

0.000889

AC:

973

AN:

1094732

Other (OTH)

AF:

0.000831

AC:

AN:

58950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

132

197

263

329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.000728

AC:

106

AN:

145566

Hom.:

Cov.:

AF XY:

0.000633

AC XY:

AN XY:

71072

show subpopulations

African (AFR)

AF:

0.000633

AC:

AN:

39486

American (AMR)

AF:

0.000273

AC:

AN:

14662

Ashkenazi Jewish (ASJ)

AF:

0.00296

AC:

AN:

3376

East Asian (EAS)

AF:

0.00205

AC:

AN:

4882

South Asian (SAS)

AF:

0.00132

AC:

AN:

4540

European-Finnish (FIN)

AF:

0.000200

AC:

AN:

10000

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.000718

AC:

AN:

65434

Other (OTH)

AF:

0.000990

AC:

AN:

2020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000473

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

PhyloP100

3.2

Mutation Taster

=38/162

disease causing

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over