Variant 9-15466848-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000380733.9(PSIP1):c.1432C>G(p.Leu478Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00054 in 1,612,400 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00033 ( 2 hom. )

Consequence

PSIP1
ENST00000380733.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0960

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0057834387).

BP6

Variant 9-15466848-G-C is Benign according to our data. Variant chr9-15466848-G-C is described in ClinVar as [Benign]. Clinvar id is 716195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 391 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSIP1	NM_033222.5 linkuse as main transcript	c.1432C>G	p.Leu478Val	missense_variant	15/16	ENST00000380733.9	NP_150091.2
PSIP1	NM_001128217.3 linkuse as main transcript	c.1432C>G	p.Leu478Val	missense_variant	15/16		NP_001121689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSIP1	ENST00000380733.9 linkuse as main transcript	c.1432C>G	p.Leu478Val	missense_variant	15/16	1	NM_033222.5	ENSP00000370109	P1	O75475-1
PSIP1	ENST00000380738.8 linkuse as main transcript	c.1432C>G	p.Leu478Val	missense_variant	15/16	1		ENSP00000370114	P1	O75475-1

Frequencies

GnomAD3 genomes

AF:

0.00256

AC:

390

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00867

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000843

AC:

210

AN:

249218

Hom.:

AF XY:

0.000623

AC XY:

AN XY:

134760

show subpopulations

Gnomad AFR exome

AF:

0.00935

Gnomad AMR exome

AF:

0.000799

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.000328

AC:

479

AN:

1460144

Hom.:

Cov.:

AF XY:

0.000266

AC XY:

193

AN XY:

726374

show subpopulations

Gnomad4 AFR exome

AF:

0.00797

Gnomad4 AMR exome

AF:

0.000857

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000379

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000356

Gnomad4 NFE exome

AF:

0.0000963

Gnomad4 OTH exome

AF:

0.000514

GnomAD4 genome

AF:

0.00257

AC:

391

AN:

152256

Hom.:

Cov.:

AF XY:

0.00265

AC XY:

197

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00867

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000490

Hom.:

Bravo

AF:

0.00299

ESP6500AA

AF:

0.00976

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000988

AC:

120

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.048

T;T

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.74

.;T

MetaRNN

Benign

0.0058

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.10

N;N

REVEL

Benign

0.047

Sift

Benign

0.84

T;T

Sift4G

Benign

0.45

T;T

Polyphen

0.0

B;B

Vest4

0.17

MVP

0.24

MPC

0.13

ClinPred

0.0054

GERP RS

0.048

Varity_R

0.038

gMVP

0.071

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