Genetic Variant NM_001114133.3: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:

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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

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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