dbSNP rs1242078354: PSIP1:p.Ser208Cys (chr9-15478484-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_033222.5(PSIP1):c.622A>T(p.Ser208Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,433,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

PSIP1
NM_033222.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.669

Variant links:

Genes affected

PSIP1 (HGNC:9527): (PC4 and SRSF1 interacting protein 1) Enables DNA-binding transcription factor binding activity; chromatin binding activity; and transcription coactivator activity. Involved in mRNA 5'-splice site recognition and positive regulation of transcription by RNA polymerase II. Located in heterochromatin; nuclear periphery; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PSIP1 links:

Genome browser will be placed here

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=0.08244303).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSIP1	NM_033222.5 link	c.622A>T	p.Ser208Cys	missense_variant	Exon 8 of 16	ENST00000380733.9	NP_150091.2	O75475-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSIP1	ENST00000380733.9 link	c.622A>T	p.Ser208Cys	missense_variant	Exon 8 of 16	1	NM_033222.5	ENSP00000370109.4		O75475-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250802

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135568

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

6.97e-7

AC:

AN:

1433694

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714812

show subpopulations

Gnomad4 AFR exome

AF:

0.0000305

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.20

T;T;.;.;.

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.026

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.83

.;T;T;.;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.082

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

N;N;N;N;N

PrimateAI

Uncertain

0.48

PROVEAN

Uncertain

-2.7

D;D;D;D;D

REVEL

Benign

0.024

Sift

Uncertain

0.0040

D;D;D;D;D

Sift4G

Uncertain

0.013

D;D;D;D;D

Polyphen

0.070

B;B;.;P;P

Vest4

0.14

MutPred

0.23

Loss of phosphorylation at S208 (P = 0.0093);Loss of phosphorylation at S208 (P = 0.0093);Loss of phosphorylation at S208 (P = 0.0093);Loss of phosphorylation at S208 (P = 0.0093);Loss of phosphorylation at S208 (P = 0.0093);

MVP

0.26

MPC

0.20

ClinPred

0.28

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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