9-15474125-G-T

Variant names:

• chr9-15474125-G-T
• rs763254518
• NM_033222.5:c.742C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_033222.5(PSIP1):​c.742C>A​(p.Pro248Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,416 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PSIP1 NM_033222.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.90
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.054445803).
• BS2: High AC in GnomAdExome4 at 24 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSIP1	NM_033222.5	MANE Select	c.742C>A	p.Pro248Thr	missense	Exon 9 of 16	NP_150091.2
	PSIP1	NM_001128217.3		c.742C>A	p.Pro248Thr	missense	Exon 9 of 16	NP_001121689.1	O75475-1
	PSIP1	NM_001438383.1		c.742C>A	p.Pro248Thr	missense	Exon 9 of 11	NP_001425312.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSIP1	ENST00000380733.9	TSL:1 MANE Select	c.742C>A	p.Pro248Thr	missense	Exon 9 of 16	ENSP00000370109.4	O75475-1
	PSIP1	ENST00000380738.8	TSL:1	c.742C>A	p.Pro248Thr	missense	Exon 9 of 16	ENSP00000370114.4	O75475-1
	PSIP1	ENST00000397519.6	TSL:1	c.742C>A	p.Pro248Thr	missense	Exon 8 of 10	ENSP00000380653.2	O75475-2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151032 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

GnomAD2 exomes AF: 0.0000399 AC: 10 AN: 250728 AF XY: 0.0000443

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461416 Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13 AN XY: 727002

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.000278 AC: 24 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111786

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151032 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73666

African (AFR) AF: 0.00 AC: 0 AN: 41048

American (AMR) AF: 0.00 AC: 0 AN: 15134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67832

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Benign	0.92
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.9
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.039
Sift	Benign	0.33	T
Sift4G	Benign	0.73	T
Polyphen		0.015	B
Vest4		0.15
MutPred		0.27		Gain of phosphorylation at P248 (P = 4e-04)
MVP		0.49
MPC		0.20
ClinPred		0.047	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.062
gMVP		0.20
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs763254518; hg19: chr9-15474123;