9-15478502-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033222.5(PSIP1):c.604C>G(p.Gln202Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,080 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PSIP1 NM_033222.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.97

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]

ACMG classification

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=0.09910646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSIP1	NM_033222.5	c.604C>G	p.Gln202Glu	missense_variant	8/16	ENST00000380733.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSIP1	ENST00000380733.9	c.604C>G	p.Gln202Glu	missense_variant	8/16	1	NM_033222.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451080 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 722546

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: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2022

The c.604C>G (p.Q202E) alteration is located in exon 8 (coding exon 7) of the PSIP1 gene. This alteration results from a C to G substitution at nucleotide position 604, causing the glutamine (Q) at amino acid position 202 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	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	22
Dann	Benign	0.22
DEOGEN2	Benign	0.042	T;T;.;.;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.018
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.099	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N;N;N;N
MutationTaster	Benign	0.99	N;N;N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.040	N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0070	B;B;.;B;B
Vest4		0.20
MutPred		0.17		Gain of ubiquitination at K201 (P = 0.0341);Gain of ubiquitination at K201 (P = 0.0341);Gain of ubiquitination at K201 (P = 0.0341);Gain of ubiquitination at K201 (P = 0.0341);Gain of ubiquitination at K201 (P = 0.0341);
MVP		0.41
MPC		0.15
ClinPred		0.57	D
GERP RS		5.9
Varity_R		0.11
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs1404580057; hg19: chr9-15478500;