Genetic Variant PSTPIP2:p.Ile15Val (chr18-46040038-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024430.4(PSTPIP2):c.43A>G(p.Ile15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000757 in 1,453,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. I15F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

PSTPIP2
NM_024430.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.593

Publications

0 publications found

Variant links:

Genes affected

PSTPIP2 (HGNC:9581): (proline-serine-threonine phosphatase interacting protein 2) Predicted to enable actin filament binding activity. Predicted to be involved in actin filament polymerization. Predicted to be located in cytoskeleton and membrane. Predicted to be active in actin filament; cytoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PSTPIP2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19176781).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSTPIP2	NM_024430.4 link	c.43A>G	p.Ile15Val	missense_variant	Exon 2 of 15	ENST00000409746.5	NP_077748.3	Q9H939-1A0A0S2Z4R2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PSTPIP2	ENST00000409746.5 link	c.43A>G	p.Ile15Val	missense_variant	Exon 2 of 15	1	NM_024430.4	ENSP00000387261.4	Q9H939-1
PSTPIP2	ENST00000589328.5 link	c.43A>G	p.Ile15Val	missense_variant	Exon 2 of 14	1		ENSP00000468622.1	Q9H939-2
PSTPIP2	ENST00000587042.1 link	n.127A>G		non_coding_transcript_exon_variant	Exon 2 of 5	2
PSTPIP2	ENST00000588801.5 link	n.138A>G		non_coding_transcript_exon_variant	Exon 2 of 9	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000757

AC:

AN:

1453624

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

722950

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33158

American (AMR)

AF:

0.00

AC:

AN:

43718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25618

East Asian (EAS)

AF:

0.00

AC:

AN:

39574

South Asian (SAS)

AF:

0.00

AC:

AN:

85180

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53100

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.00000903

AC:

AN:

1107496

Other (OTH)

AF:

0.0000166

AC:

AN:

60062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000314

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.080

.;T

Eigen

Benign

0.046

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.0081

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.4

M;M

PhyloP100

0.59

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.89

.;N

REVEL

Benign

0.090

Sift

Benign

0.050

.;D

Sift4G

Benign

0.065

T;T

Polyphen

0.70

P;P

Vest4

0.26

MutPred

0.53

Loss of MoRF binding (P = 0.2355);Loss of MoRF binding (P = 0.2355);

MVP

0.37

MPC

0.45

ClinPred

0.56

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.060

gMVP

0.40

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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chr18-46040038-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over