rs61744944

chr9-15468635-T-Achr9-15468635-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_033222.5(PSIP1):c.1415A>T(p.Gln472Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00321 in 1,613,878 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (60 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (75 hom.)
• Consequence: PSIP1 NM_033222.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.89

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024690926).
• BP6: Variant 9-15468635-T-A is Benign according to our data. Variant chr9-15468635-T-A is described in ClinVar as [Benign]. Clinvar id is 790063.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSIP1	NM_033222.5	c.1415A>T	p.Gln472Leu	missense_variant	14/16	ENST00000380733.9
PSIP1	NM_001128217.3	c.1415A>T	p.Gln472Leu	missense_variant	14/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSIP1	ENST00000380733.9	c.1415A>T	p.Gln472Leu	missense_variant	14/16	1	NM_033222.5	P1
PSIP1	ENST00000380738.8	c.1415A>T	p.Gln472Leu	missense_variant	14/16	1		P1

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2531 AN: 152204 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00870

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00440 AC: 1106 AN: 251186 Hom.: 36 AF XY: 0.00325 AC XY: 441 AN XY: 135758

Gnomad AFR exome AF: 0.0572

Gnomad AMR exome AF: 0.00353

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000299

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00181 AC: 2645 AN: 1461556 Hom.: 75 Cov.: 32 AF XY: 0.00155 AC XY: 1130 AN XY: 727092

Gnomad4 AFR exome AF: 0.0580

Gnomad4 AMR exome AF: 0.00414

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000200

Gnomad4 OTH exome AF: 0.00437

GnomAD4 genome AF: 0.0167 AC: 2541 AN: 152322 Hom.: 60 Cov.: 32 AF XY: 0.0160 AC XY: 1195 AN XY: 74500

Gnomad4 AFR AF: 0.0567

Gnomad4 AMR AF: 0.00869

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.00116 Hom.: 2

Bravo AF: 0.0195

ESP6500AA AF: 0.0574 AC: 253

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00559 AC: 679

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000474

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

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.48
Cadd	Uncertain	25
Dann	Uncertain	0.98
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.046
FATHMM_MKL	Uncertain	0.94	D
MetaRNN	Benign	0.0025	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	0.90	D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.024
Sift	Uncertain	0.012	D;D
Sift4G	Benign	0.25	T;T
Polyphen		0.079	B;B
Vest4		0.44
MVP		0.41
MPC		0.13
ClinPred		0.018	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.17

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: rs61744944; hg19: chr9-15468633; COSMIC: COSV99062547; COSMIC: COSV99062547;