chr9-15466838-C-T

Position:

• chr9-15466838-C-T

Variant summary

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

The NM_033222.5(PSIP1):​c.1442G>A​(p.Gly481Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,656 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PSIP1 NM_033222.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.64

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSIP1	NM_033222.5	c.1442G>A	p.Gly481Glu	missense_variant	15/16	ENST00000380733.9	NP_150091.2
PSIP1	NM_001128217.3	c.1442G>A	p.Gly481Glu	missense_variant	15/16		NP_001121689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSIP1	ENST00000380733.9	c.1442G>A	p.Gly481Glu	missense_variant	15/16	1	NM_033222.5	ENSP00000370109.4
PSIP1	ENST00000380738.8	c.1442G>A	p.Gly481Glu	missense_variant	15/16	1		ENSP00000370114.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460656 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726614

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: 0.00000180

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

Oct 09, 2024

The c.1442G>A (p.G481E) alteration is located in exon 15 (coding exon 14) of the PSIP1 gene. This alteration results from a G to A substitution at nucleotide position 1442, causing the glycine (G) at amino acid position 481 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	0.14
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	T;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.74	.;T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;M
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.38	N;N
REVEL	Benign	0.22
Sift	Benign	0.89	T;T
Sift4G	Benign	0.54	T;T
Polyphen		0.99	D;D
Vest4		0.61
MutPred		0.13		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.79
MPC		0.69
ClinPred		0.74	D
GERP RS		5.5
Varity_R		0.12
gMVP		0.064

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: chr9-15466836;