Variant 9-15474024-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000380733.9(PSIP1):c.843T>A(p.Asp281Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0000014 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

PSIP1
ENST00000380733.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.884

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 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=0.062434077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSIP1	NM_033222.5 linkuse as main transcript	c.843T>A	p.Asp281Glu	missense_variant	9/16	ENST00000380733.9	NP_150091.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSIP1	ENST00000380733.9 linkuse as main transcript	c.843T>A	p.Asp281Glu	missense_variant	9/16	1	NM_033222.5	ENSP00000370109	P1	O75475-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000137

AC:

AN:

1460592

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726626

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

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

Aug 02, 2021

The c.843T>A (p.D281E) alteration is located in exon 9 (coding exon 8) of the PSIP1 gene. This alteration results from a T to A substitution at nucleotide position 843, causing the aspartic acid (D) at amino acid position 281 to be replaced by a glutamic acid (E). 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

0.074

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.049

T;T;.;.;.

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.74

.;T;T;.;T

M_CAP

Benign

0.059

MetaRNN

Benign

0.062

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.63

N;N;N;N;N

MutationTaster

Benign

0.97

N;N;N;N;N

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.77

N;N;N;N;N

REVEL

Benign

0.089

Sift

Benign

0.87

T;T;T;T;T

Sift4G

Benign

0.70

T;T;T;T;T

Polyphen

0.0010

B;B;.;B;B

Vest4

0.045

MutPred

0.091

Gain of ubiquitination at K286 (P = 0.1062);Gain of ubiquitination at K286 (P = 0.1062);Gain of ubiquitination at K286 (P = 0.1062);Gain of ubiquitination at K286 (P = 0.1062);Gain of ubiquitination at K286 (P = 0.1062);

MVP

0.48

MPC

0.13

ClinPred

0.32

GERP RS

4.2

Varity_R

0.045

gMVP

0.024

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over