rs35678110

chr9-15466848-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_033222.5(PSIP1):c.1432C>G(p.Leu478Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00054 in 1,612,400 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00033 (2 hom.)
• Consequence: PSIP1 NM_033222.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0960

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0057834387).
• BP6: Variant 9-15466848-G-C is Benign according to our data. Variant chr9-15466848-G-C is described in ClinVar as [Benign]. Clinvar id is 716195.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 390 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSIP1	NM_033222.5	c.1432C>G	p.Leu478Val	missense_variant	15/16	ENST00000380733.9
PSIP1	NM_001128217.3	c.1432C>G	p.Leu478Val	missense_variant	15/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSIP1	ENST00000380733.9	c.1432C>G	p.Leu478Val	missense_variant	15/16	1	NM_033222.5	P1
PSIP1	ENST00000380738.8	c.1432C>G	p.Leu478Val	missense_variant	15/16	1		P1

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 390 AN: 152138 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00867

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000843 AC: 210 AN: 249218 Hom.: 1 AF XY: 0.000623 AC XY: 84 AN XY: 134760

Gnomad AFR exome AF: 0.00935

Gnomad AMR exome AF: 0.000799

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.000496

GnomAD4 exome AF: 0.000328 AC: 479 AN: 1460144 Hom.: 2 Cov.: 30 AF XY: 0.000266 AC XY: 193 AN XY: 726374

Gnomad4 AFR exome AF: 0.00797

Gnomad4 AMR exome AF: 0.000857

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000379

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000356

Gnomad4 NFE exome AF: 0.0000963

Gnomad4 OTH exome AF: 0.000514

GnomAD4 genome AF: 0.00257 AC: 391 AN: 152256 Hom.: 0 Cov.: 33 AF XY: 0.00265 AC XY: 197 AN XY: 74450

Gnomad4 AFR AF: 0.00867

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000754

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000490 Hom.: 0

Bravo AF: 0.00299

ESP6500AA AF: 0.00976 AC: 43

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000988 AC: 120

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	14
Dann	Uncertain	0.98
DEOGEN2	Benign	0.048	T;T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.23	N
MetaRNN	Benign	0.0058	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.10	N;N
REVEL	Benign	0.047
Sift	Benign	0.84	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.0	B;B
Vest4		0.17
MVP		0.24
MPC		0.13
ClinPred		0.0054	T
GERP RS		0.048
Varity_R		0.038
gMVP		0.071

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

Other links and lift over

dbSNP: rs35678110; hg19: chr9-15466846;