Genetic Variant PSIP1:p.Ala484Pro (chr9-15466830-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_033222.5(PSIP1):c.1450G>C(p.Ala484Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,613,192 control chromosomes in the GnomAD database, including 2 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00079 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000061 ( 1 hom. )

Consequence

PSIP1
NM_033222.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.204

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:

SNAPC3 (HGNC:11136): (small nuclear RNA activating complex polypeptide 3) Predicted to enable RNA polymerase III type 3 promoter sequence-specific DNA binding activity and bent DNA binding activity. Predicted to contribute to RNA polymerase II cis-regulatory region sequence-specific DNA binding activity and core promoter sequence-specific DNA binding activity. Predicted to be involved in snRNA transcription by RNA polymerase II and snRNA transcription by RNA polymerase III. Located in nuclear body and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

SNAPC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058037937).

BP6

Variant 9-15466830-C-G is Benign according to our data. Variant chr9-15466830-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 749768.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 121 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSIP1	NM_033222.5 link	c.1450G>C	p.Ala484Pro	missense_variant	Exon 15 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.1450G>C	p.Ala484Pro	missense_variant	Exon 15 of 16	1	NM_033222.5	ENSP00000370109.4		O75475-1
PSIP1	ENST00000380738.8 link	c.1450G>C	p.Ala484Pro	missense_variant	Exon 15 of 16	1		ENSP00000370114.4		O75475-1

Frequencies

GnomAD3 genomes

AF:

0.000762

AC:

116

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000180

AC:

AN:

249816

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

135084

show subpopulations

Gnomad AFR exome

AF:

0.00235

Gnomad AMR exome

AF:

0.000147

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:

0.00000883

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000609

AC:

AN:

1460894

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

726754

show subpopulations

Gnomad4 AFR exome

AF:

0.00209

Gnomad4 AMR exome

AF:

0.000180

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:

0.00000270

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000794

AC:

121

AN:

152298

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00269

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000127

Hom.:

Bravo

AF:

0.000691

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000272

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 21, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.052

T;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.75

.;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.0058

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.22

N;N

REVEL

Benign

0.11

Sift

Benign

0.23

T;T

Sift4G

Benign

0.30

T;T

Polyphen

0.74

P;P

Vest4

0.35

MVP

0.43

MPC

0.22

ClinPred

0.012

GERP RS

4.5

Varity_R

0.080

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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