NM_033222.5:c.836G>A

Variant names:

• chr9-15474031-C-T
• NM_033222.5:c.836G>A

Variant summary

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

The NM_033222.5(PSIP1):​c.836G>A​(p.Gly279Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 2.59

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=0.10505667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSIP1	NM_033222.5	c.836G>A	p.Gly279Glu	missense_variant	Exon 9 of 16	ENST00000380733.9	NP_150091.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSIP1	ENST00000380733.9	c.836G>A	p.Gly279Glu	missense_variant	Exon 9 of 16	1	NM_033222.5	ENSP00000370109.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460988 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726788

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.062	T;T;.;.;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	.;T;T;.;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;L;L;L;L
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.1	N;N;N;N;N
REVEL	Benign	0.022
Sift	Benign	0.12	T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0010	B;B;.;B;B
Vest4		0.37
MutPred		0.16		Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);
MVP		0.24
MPC		0.69
ClinPred		0.58	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.060
gMVP		0.083

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-15474029;