Genetic Variant NM_001114133.3:c.2464C>T (chr10-73647188-G-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.2464C>T(p.Pro822Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,694 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SYNPO2L
NM_001114133.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

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:

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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.2464C>T	p.Pro822Ser	missense	Exon 4 of 4	NP_001107605.1	Q9H987-1
	SYNPO2L	NM_024875.5		c.1792C>T	p.Pro598Ser	missense	Exon 2 of 2	NP_079151.2	Q9H987-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNPO2L	ENST00000394810.3	TSL:1 MANE Select	c.2464C>T	p.Pro822Ser	missense	Exon 4 of 4	ENSP00000378289.2	Q9H987-1
	SYNPO2L	ENST00000372873.8	TSL:1	c.1792C>T	p.Pro598Ser	missense	Exon 2 of 2	ENSP00000361964.4	Q9H987-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000798

AC:

AN:

250496

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461694

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111884

Other (OTH)

AF:

0.0000166

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.47

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.83

M_CAP

Benign

0.048

MetaRNN

Uncertain

0.68

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.5

PhyloP100

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-6.1

REVEL

Uncertain

0.58

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.55

MVP

0.78

MPC

1.2

ClinPred

1.0

GERP RS

5.1

Varity_R

0.55

gMVP

0.65

Mutation Taster

=58/42

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over