Genetic Variant SYNPO2L:c.*335T>G (chr10-73646383-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001114133.3(SYNPO2L):c.*335T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,034,624 control chromosomes in the GnomAD database, including 14,696 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 4262 hom., cov: 31)

Exomes 𝑓: 0.15 ( 10434 hom. )

Consequence

SYNPO2L
NM_001114133.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.517

Publications

21 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNPO2L	NM_001114133.3 link	c.*335T>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000394810.3	NP_001107605.1	Q9H987-1
SYNPO2L	NM_024875.5 link	c.*335T>G		3_prime_UTR_variant	Exon 2 of 2		NP_079151.2	Q9H987-2A0A024QZQ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNPO2L	ENST00000394810.3 link	c.*335T>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_001114133.3	ENSP00000378289.2		Q9H987-1
SYNPO2L	ENST00000372873.8 link	c.*335T>G		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000361964.4		Q9H987-2

Frequencies

GnomAD3 genomes

AF:

0.211

AC:

32029

AN:

151854

Hom.:

4255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.379

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.204

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.180

GnomAD4 exome

AF:

0.149

AC:

131206

AN:

882652

Hom.:

10434

Cov.:

AF XY:

0.148

AC XY:

60737

AN XY:

409526

show subpopulations

African (AFR)

AF:

0.382

AC:

6723

AN:

17622

American (AMR)

AF:

0.119

AC:

326

AN:

2740

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

1536

AN:

7078

East Asian (EAS)

AF:

0.211

AC:

1474

AN:

6988

South Asian (SAS)

AF:

0.221

AC:

3785

AN:

17100

European-Finnish (FIN)

AF:

0.139

AC:

416

AN:

2992

Middle Eastern (MID)

AF:

0.175

AC:

331

AN:

1892

European-Non Finnish (NFE)

AF:

0.140

AC:

111474

AN:

795616

Other (OTH)

AF:

0.168

AC:

5141

AN:

30624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

7098

14195

21293

28390

35488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5520

11040

16560

22080

27600

<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:

0.211

AC:

32067

AN:

151972

Hom.:

4262

Cov.:

AF XY:

0.208

AC XY:

15432

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.378

AC:

15669

AN:

41416

American (AMR)

AF:

0.131

AC:

1994

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.220

AC:

762

AN:

3470

East Asian (EAS)

AF:

0.204

AC:

1053

AN:

5172

South Asian (SAS)

AF:

0.209

AC:

1008

AN:

4824

European-Finnish (FIN)

AF:

0.134

AC:

1410

AN:

10560

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.141

AC:

9580

AN:

67964

Other (OTH)

AF:

0.178

AC:

374

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1171

2341

3512

4682

5853

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.165

Hom.:

3307

Bravo

AF:

0.221

Asia WGS

AF:

0.177

AC:

620

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

9.6

(source)

DANN

Benign

0.83

PhyloP100

0.52

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over