NM_033222.5:c.1152G>C

Variant names:

• chr9-15469011-C-G
• NM_033222.5:c.1152G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033222.5(PSIP1):​c.1152G>C​(p.Gln384His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 6.8e-7 (0 hom.)
• Consequence: PSIP1 NM_033222.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29764616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSIP1	NM_033222.5	c.1152G>C	p.Gln384His	missense_variant	Exon 13 of 16	ENST00000380733.9	NP_150091.2
PSIP1	NM_001128217.3	c.1152G>C	p.Gln384His	missense_variant	Exon 13 of 16		NP_001121689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSIP1	ENST00000380733.9	c.1152G>C	p.Gln384His	missense_variant	Exon 13 of 16	1	NM_033222.5	ENSP00000370109.4
PSIP1	ENST00000380738.8	c.1152G>C	p.Gln384His	missense_variant	Exon 13 of 16	1		ENSP00000370114.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461666 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727128

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: 8.99e-7

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	Pathogenic	0.57
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.87	.;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.13
Sift	Benign	0.069	T;T
Sift4G	Uncertain	0.056	T;T
Polyphen		0.48	P;P
Vest4		0.44
MutPred		0.37		Gain of loop (P = 0.002);Gain of loop (P = 0.002);
MVP		0.46
MPC		0.58
ClinPred		0.85	D
GERP RS		4.4
Varity_R		0.62
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr9-15469009;