9-15468635-T-G

Position:

• chr9-15468635-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033222.5(PSIP1):​c.1415A>C​(p.Gln472Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,560 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PSIP1 NM_033222.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.89

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12199575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSIP1	NM_033222.5	c.1415A>C	p.Gln472Pro	missense_variant	14/16	ENST00000380733.9	NP_150091.2
PSIP1	NM_001128217.3	c.1415A>C	p.Gln472Pro	missense_variant	14/16		NP_001121689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSIP1	ENST00000380733.9	c.1415A>C	p.Gln472Pro	missense_variant	14/16	1	NM_033222.5	ENSP00000370109.4
PSIP1	ENST00000380738.8	c.1415A>C	p.Gln472Pro	missense_variant	14/16	1		ENSP00000370114.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251186 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135758

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 SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461560 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727092

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.067	T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.62	.;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.96	N;N
REVEL	Benign	0.11
Sift	Benign	0.35	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.0	B;B
Vest4		0.43
MutPred		0.12		Loss of MoRF binding (P = 0.0444);Loss of MoRF binding (P = 0.0444);
MVP		0.59
MPC		0.16
ClinPred		0.14	T
GERP RS		4.4
Varity_R		0.20
gMVP		0.16

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

LitVar

Other links and lift over

dbSNP: rs61744944; hg19: chr9-15468633;