Genetic Variant PSIP1:c.393+104C>G (chr9-15486723-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033222.5(PSIP1):c.393+104C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 796,340 control chromosomes in the GnomAD database, including 310,342 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 0.89 ( 60746 hom., cov: 32)

Exomes 𝑓: 0.88 ( 249596 hom. )

Consequence

PSIP1
NM_033222.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.486

Publications

6 publications found

Variant links:

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]

PSIP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033222.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PSIP1	NM_033222.5	MANE Select	c.393+104C>G	intron	N/A	NP_150091.2
PSIP1	NM_001128217.3		c.393+104C>G	intron	N/A	NP_001121689.1
PSIP1	NM_001438383.1		c.393+104C>G	intron	N/A	NP_001425312.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PSIP1	ENST00000380733.9	TSL:1 MANE Select	c.393+104C>G	intron	N/A	ENSP00000370109.4
PSIP1	ENST00000380738.8	TSL:1	c.393+104C>G	intron	N/A	ENSP00000370114.4
PSIP1	ENST00000397519.6	TSL:1	c.393+104C>G	intron	N/A	ENSP00000380653.2

Frequencies

GnomAD3 genomes

AF:

0.892

AC:

135670

AN:

152100

Hom.:

60703

Cov.:

show subpopulations

Gnomad AFR

AF:

0.898

Gnomad AMI

AF:

0.965

Gnomad AMR

AF:

0.922

Gnomad ASJ

AF:

0.865

Gnomad EAS

AF:

0.777

Gnomad SAS

AF:

0.671

Gnomad FIN

AF:

0.884

Gnomad MID

AF:

0.886

Gnomad NFE

AF:

0.907

Gnomad OTH

AF:

0.907

GnomAD4 exome

AF:

0.877

AC:

565108

AN:

644122

Hom.:

249596

AF XY:

0.868

AC XY:

299476

AN XY:

344884

show subpopulations

African (AFR)

AF:

0.898

AC:

12927

AN:

14402

American (AMR)

AF:

0.926

AC:

21169

AN:

22868

Ashkenazi Jewish (ASJ)

AF:

0.862

AC:

16195

AN:

18786

East Asian (EAS)

AF:

0.772

AC:

25072

AN:

32482

South Asian (SAS)

AF:

0.681

AC:

38892

AN:

57128

European-Finnish (FIN)

AF:

0.885

AC:

39112

AN:

44200

Middle Eastern (MID)

AF:

0.853

AC:

2137

AN:

2504

European-Non Finnish (NFE)

AF:

0.909

AC:

380705

AN:

419040

Other (OTH)

AF:

0.883

AC:

28899

AN:

32712

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

3106

6212

9317

12423

15529

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3838

7676

11514

15352

19190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.892

AC:

135767

AN:

152218

Hom.:

60746

Cov.:

AF XY:

0.887

AC XY:

66029

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.898

AC:

37329

AN:

41552

American (AMR)

AF:

0.922

AC:

14108

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.865

AC:

3003

AN:

3472

East Asian (EAS)

AF:

0.776

AC:

4002

AN:

5154

South Asian (SAS)

AF:

0.670

AC:

3231

AN:

4822

European-Finnish (FIN)

AF:

0.884

AC:

9360

AN:

10594

Middle Eastern (MID)

AF:

0.878

AC:

258

AN:

294

European-Non Finnish (NFE)

AF:

0.907

AC:

61685

AN:

68008

Other (OTH)

AF:

0.905

AC:

1911

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

718

1436

2154

2872

3590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.879

Hom.:

2825

Bravo

AF:

0.900

Asia WGS

AF:

0.738

AC:

2569

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.64

(source)

DANN

Benign

0.65

PhyloP100

-0.49

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over