dbSNP rs148367718: SYNPO2L:p.Pro797Ser (chr10-73647263-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001114133.3(SYNPO2L):c.2389C>T(p.Pro797Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P797A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

SYNPO2L
NM_001114133.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.524

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029407233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNPO2L	NM_001114133.3 link	c.2389C>T	p.Pro797Ser	missense_variant	Exon 4 of 4	ENST00000394810.3	NP_001107605.1	Q9H987-1
SYNPO2L	NM_024875.5 link	c.1717C>T	p.Pro573Ser	missense_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.2389C>T	p.Pro797Ser	missense_variant	Exon 4 of 4	1	NM_001114133.3	ENSP00000378289.2		Q9H987-1
SYNPO2L	ENST00000372873.8 link	c.1717C>T	p.Pro573Ser	missense_variant	Exon 2 of 2	1		ENSP00000361964.4		Q9H987-2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251412

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152086

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.19

DANN

Benign

0.81

DEOGEN2

Benign

0.0042

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.029

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.53

.;N

PrimateAI

Benign

0.45

PROVEAN

Benign

0.45

N;N

REVEL

Benign

0.032

Sift

Benign

0.61

T;T

Sift4G

Benign

0.78

T;T

Polyphen

0.0

B;B

Vest4

0.11

MutPred

0.20

.;Gain of phosphorylation at P797 (P = 0.0191);

MVP

0.16

MPC

0.38

ClinPred

0.026

GERP RS

0.69

Varity_R

0.029

gMVP

0.22

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over