9-15510109-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_033222.5(PSIP1):c.72+8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,601,626 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (29 hom., cov: 31)
  • Exomes 𝑓: 0.0013 (28 hom.)
• Consequence: PSIP1 NM_033222.5 splice_region, intron
• Scores: Splicing: ADA: 0.0009380
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.808

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 9-15510109-T-C is Benign according to our data. Variant chr9-15510109-T-C is described in ClinVar as [Benign]. Clinvar id is 776764.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0109 (1655/152234) while in subpopulation AFR AF= 0.037 (1537/41538). AF 95% confidence interval is 0.0355. There are 29 homozygotes in gnomad4. There are 792 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 1647 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSIP1	NM_033222.5	c.72+8A>G		splice_region_variant, intron_variant		ENST00000380733.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSIP1	ENST00000380733.9	c.72+8A>G		splice_region_variant, intron_variant		1	NM_033222.5	P1

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1647 AN: 152116 Hom.: 29 Cov.: 31

Gnomad AFR AF: 0.0369

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00863

GnomAD3 exomes AF: 0.00284 AC: 686 AN: 241704 Hom.: 9 AF XY: 0.00192 AC XY: 251 AN XY: 131010

Gnomad AFR exome AF: 0.0376

Gnomad AMR exome AF: 0.00249

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000136

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000380

Gnomad OTH exome AF: 0.00206

GnomAD4 exome AF: 0.00131 AC: 1899 AN: 1449392 Hom.: 28 Cov.: 31 AF XY: 0.00116 AC XY: 834 AN XY: 721212

Gnomad4 AFR exome AF: 0.0393

Gnomad4 AMR exome AF: 0.00302

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000130

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000265

Gnomad4 OTH exome AF: 0.00294

GnomAD4 genome AF: 0.0109 AC: 1655 AN: 152234 Hom.: 29 Cov.: 31 AF XY: 0.0106 AC XY: 792 AN XY: 74438

Gnomad4 AFR AF: 0.0370

Gnomad4 AMR AF: 0.00529

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00854

Alfa AF: 0.00589 Hom.: 5

Bravo AF: 0.0123

Asia WGS AF: 0.00260 AC: 9 AN: 3478

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	15
Dann	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00094
dbscSNV1_RF	Benign	0.0060
SpliceAI score (max)		0.16		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: rs147272916; hg19: chr9-15510107;