dbSNP rs768606281: SYNPO2L:p.Pro707LeufsTer11 (chr10-73647531-AG-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001114133.3(SYNPO2L):c.2120delC(p.Pro707LeufsTer11) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 1,580,240 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

SYNPO2L
NM_001114133.3 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.2120delC	p.Pro707LeufsTer11	frameshift	Exon 4 of 4	NP_001107605.1	Q9H987-1
	SYNPO2L	NM_024875.5		c.1448delC	p.Pro483LeufsTer11	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.2120delC	p.Pro707LeufsTer11	frameshift	Exon 4 of 4	ENSP00000378289.2	Q9H987-1
SYNPO2L	ENST00000372873.8	TSL:1	c.1448delC	p.Pro483LeufsTer11	frameshift	Exon 2 of 2	ENSP00000361964.4	Q9H987-2
SYNPO2L-AS1	ENST00000759288.1		n.10delG		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000137

AC:

AN:

145460

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000508

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000423

AC:

AN:

236560

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000638

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000139

AC:

AN:

1434780

Hom.:

Cov.:

AF XY:

0.0000197

AC XY:

AN XY:

710496

show subpopulations

African (AFR)

AF:

0.0000917

AC:

AN:

32712

American (AMR)

AF:

0.00

AC:

AN:

42632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24750

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39158

South Asian (SAS)

AF:

0.0000119

AC:

AN:

83694

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5624

European-Non Finnish (NFE)

AF:

0.0000128

AC:

AN:

1094734

Other (OTH)

AF:

0.0000170

AC:

AN:

58950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000137

AC:

AN:

145460

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

70958

show subpopulations

African (AFR)

AF:

0.0000508

AC:

AN:

39364

American (AMR)

AF:

0.00

AC:

AN:

14642

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3376

East Asian (EAS)

AF:

0.00

AC:

AN:

4896

South Asian (SAS)

AF:

0.00

AC:

AN:

4552

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10000

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65442

Other (OTH)

AF:

0.00

AC:

AN:

2002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.2

Mutation Taster

=30/170

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over