Variant 10-73648267-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001114133.3(SYNPO2L):c.1385G>T(p.Ser462Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000967 in 1,447,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

SYNPO2L
NM_001114133.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.448

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08876288).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNPO2L	NM_001114133.3 link	c.1385G>T	p.Ser462Ile	missense_variant	4/4	ENST00000394810.3	NP_001107605.1	Q9H987-1
SYNPO2L	NM_024875.5 link	c.713G>T	p.Ser238Ile	missense_variant	2/2		NP_079151.2	Q9H987-2A0A024QZQ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNPO2L	ENST00000394810.3 link	c.1385G>T	p.Ser462Ile	missense_variant	4/4	1	NM_001114133.3	ENSP00000378289.2		Q9H987-1
SYNPO2L	ENST00000372873.8 link	c.713G>T	p.Ser238Ile	missense_variant	2/2	1		ENSP00000361964.4		Q9H987-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000296

AC:

AN:

236618

Hom.:

AF XY:

0.0000309

AC XY:

AN XY:

129484

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000331

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.00000967

AC:

AN:

1447382

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

719994

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000303

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2023

The c.1385G>T (p.S462I) alteration is located in exon 4 (coding exon 4) of the SYNPO2L gene. This alteration results from a G to T substitution at nucleotide position 1385, causing the serine (S) at amino acid position 462 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.022

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.089

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

.;M

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.077

Sift

Uncertain

0.014

D;D

Sift4G

Uncertain

0.051

T;D

Polyphen

0.57

P;B

Vest4

0.18

MutPred

0.35

.;Loss of glycosylation at S462 (P = 0.0043);

MVP

0.39

MPC

0.53

ClinPred

0.048

GERP RS

1.9

Varity_R

0.11

gMVP

0.62

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over