9-15509368-G-C

Position:

• chr9-15509368-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_033222.5(PSIP1):​c.72+749C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 151,990 control chromosomes in the GnomAD database, including 11,248 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (11248 hom., cov: 32)
• Consequence: PSIP1 NM_033222.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSIP1	NM_033222.5	c.72+749C>G		intron_variant		ENST00000380733.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSIP1	ENST00000380733.9	c.72+749C>G		intron_variant		1	NM_033222.5	P1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52132 AN: 151872 Hom.: 11244 Cov.: 32

Gnomad AFR AF: 0.0832

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.384

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.343 AC: 52135 AN: 151990 Hom.: 11248 Cov.: 32 AF XY: 0.354 AC XY: 26293 AN XY: 74268

Gnomad4 AFR AF: 0.0830

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.383

Alfa AF: 0.257 Hom.: 782

Bravo AF: 0.337

Asia WGS AF: 0.454 AC: 1579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.37
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.35		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7470146; hg19: chr9-15509366; COSMIC: COSV66255556;