chr9-15466830-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_033222.5(PSIP1):c.1450G>C(p.Ala484Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,613,192 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00079 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000061 ( 1 hom. )

Consequence

PSIP1
NM_033222.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.204

Publications

0 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:

SNAPC3 (HGNC:11136): (small nuclear RNA activating complex polypeptide 3) Predicted to enable RNA polymerase III type 3 promoter sequence-specific DNA binding activity and bent DNA binding activity. Predicted to contribute to RNA polymerase II cis-regulatory region sequence-specific DNA binding activity and core promoter sequence-specific DNA binding activity. Predicted to be involved in snRNA transcription by RNA polymerase II and snRNA transcription by RNA polymerase III. Located in nuclear body and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

SNAPC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058037937).

BP6

Variant 9-15466830-C-G is Benign according to our data. Variant chr9-15466830-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 749768.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 121 AD gene.

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	HGVSp	Effect	Exon Rank	Protein	UniProt
PSIP1	NM_033222.5	MANE Select	c.1450G>C	p.Ala484Pro	missense	Exon 15 of 16	NP_150091.2
PSIP1	NM_001128217.3		c.1450G>C	p.Ala484Pro	missense	Exon 15 of 16	NP_001121689.1	O75475-1
SNAPC3	NM_001369648.2		c.*5163C>G		downstream_gene	N/A	NP_001356577.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSIP1	ENST00000380733.9	TSL:1 MANE Select	c.1450G>C	p.Ala484Pro	missense	Exon 15 of 16	ENSP00000370109.4	O75475-1
PSIP1	ENST00000380738.8	TSL:1	c.1450G>C	p.Ala484Pro	missense	Exon 15 of 16	ENSP00000370114.4	O75475-1
PSIP1	ENST00000950213.1		c.1486G>C	p.Ala496Pro	missense	Exon 15 of 16	ENSP00000620272.1

Frequencies

GnomAD3 genomes

AF:

0.000762

AC:

116

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000180

AC:

AN:

249816

AF XY:

0.000141

show subpopulations

Gnomad AFR exome

AF:

0.00235

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000609

AC:

AN:

1460894

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

726754

show subpopulations

African (AFR)

AF:

0.00209

AC:

AN:

33414

American (AMR)

AF:

0.000180

AC:

AN:

44506

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39640

South Asian (SAS)

AF:

0.00

AC:

AN:

86010

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111684

Other (OTH)

AF:

0.000116

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000794

AC:

121

AN:

152298

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00269

AC:

112

AN:

41562

American (AMR)

AF:

0.000392

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000127

Hom.:

Bravo

AF:

0.000691

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000272

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.052

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.75

M_CAP

Benign

0.010

MetaRNN

Benign

0.0058

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

-0.20

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.22

REVEL

Benign

0.11

Sift

Benign

0.23

Sift4G

Benign

0.30

Polyphen

0.74

Vest4

0.35

MVP

0.43

MPC

0.22

ClinPred

0.012

GERP RS

4.5

Varity_R

0.080

gMVP

0.10

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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