9-15465534-T-C

Position:

chr9-15465534-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BP4_StrongBS2

The ENST00000380733.9(PSIP1):c.1579A>G(p.Thr527Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000386 in 1,424,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

PSIP1
ENST00000380733.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0910

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 Likely_benign. Variant got -6 ACMG points.

PM1

In a modified_residue Phosphothreonine (size 0) in uniprot entity PSIP1_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.036054432).

BS2

High AC in GnomAdExome4 at 55 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSIP1	NM_033222.5 linkuse as main transcript	c.1579A>G	p.Thr527Ala	missense_variant	16/16	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.1579A>G	p.Thr527Ala	missense_variant	16/16	1	NM_033222.5	ENSP00000370109	P1	O75475-1
PSIP1	ENST00000380738.8 linkuse as main transcript	c.1579A>G	p.Thr527Ala	missense_variant	16/16	1		ENSP00000370114	P1	O75475-1
SNAPC3	ENST00000610884.4 linkuse as main transcript	c.*773T>C		3_prime_UTR_variant	12/12	1		ENSP00000483273	P1
SNAPC3	ENST00000467062.5 linkuse as main transcript	c.*773T>C		3_prime_UTR_variant, NMD_transcript_variant	12/12	1		ENSP00000436699

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000163

AC:

AN:

246114

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000341

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000386

AC:

AN:

1424700

Hom.:

Cov.:

AF XY:

0.0000366

AC XY:

AN XY:

710256

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:

0.0000474

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000453

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000731

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

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

Feb 16, 2023

The c.1579A>G (p.T527A) alteration is located in exon 16 (coding exon 15) of the PSIP1 gene. This alteration results from a A to G substitution at nucleotide position 1579, causing the threonine (T) at amino acid position 527 to be replaced by an alanine (A). 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

0.054

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.059

T;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.51

.;T

M_CAP

Benign

0.0080

MetaRNN

Benign

0.036

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.28

N;N

REVEL

Benign

0.061

Sift

Benign

0.26

T;T

Sift4G

Benign

0.78

T;T

Polyphen

0.0

B;B

Vest4

0.050

MutPred

0.076

Loss of phosphorylation at T527 (P = 0.0285);Loss of phosphorylation at T527 (P = 0.0285);

MVP

0.38

MPC

0.13

ClinPred

0.022

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.021

gMVP

0.062

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