9-15466806-G-T

Variant summary

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

The NM_033222.5(PSIP1):c.1474C>A(p.His492Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000014 (0 hom.)
• Consequence: PSIP1 NM_033222.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.46

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=0.19837826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSIP1	NM_033222.5	c.1474C>A	p.His492Asn	missense_variant	15/16	ENST00000380733.9
PSIP1	NM_001128217.3	c.1474C>A	p.His492Asn	missense_variant	15/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSIP1	ENST00000380733.9	c.1474C>A	p.His492Asn	missense_variant	15/16	1	NM_033222.5	P1
PSIP1	ENST00000380738.8	c.1474C>A	p.His492Asn	missense_variant	15/16	1		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461110 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726850

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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 01, 2023

The c.1474C>A (p.H492N) alteration is located in exon 15 (coding exon 14) of the PSIP1 gene. This alteration results from a C to A substitution at nucleotide position 1474, causing the histidine (H) at amino acid position 492 to be replaced by an asparagine (N). 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	0.059
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.47
Cadd	Uncertain	23
Dann	Benign	0.96
DEOGEN2	Benign	0.050	T;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.039
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	0.72	D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.88	N;N
REVEL	Benign	0.043
Sift	Uncertain	0.012	D;D
Sift4G	Benign	0.15	T;T
Polyphen		0.012	B;B
Vest4		0.48
MutPred		0.091		Gain of phosphorylation at S496 (P = 0.4448);Gain of phosphorylation at S496 (P = 0.4448);
MVP		0.50
MPC		0.60
ClinPred		0.88	D
GERP RS		4.4
Varity_R		0.18
gMVP		0.10

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-15466804;