rs104894037

Positions:

• chr7-33096550-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_203288.2(RP9):​c.410A>T​(p.His137Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RP9 NM_203288.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 6.15

Genes affected

RP9 (HGNC:10288): (RP9 pre-mRNA splicing factor) The protein encoded by this gene can be bound and phosphorylated by the protooncogene PIM1 product, a serine/threonine protein kinase . This protein localizes in nuclear speckles containing the splicing factors, and has a role in pre-mRNA splicing. CBF1-interacting protein (CIR), a corepressor of CBF1, can also bind to this protein and effects alternative splicing. Mutations in this gene result in autosomal dominant retinitis pigmentosa-9. This gene has a pseudogene (GeneID: 441212), which is located in tandem array approximately 166 kb distal to this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.921

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RP9	NM_203288.2	c.410A>T	p.His137Leu	missense_variant	5/6	ENST00000297157.8
RP9	XM_011515468.4	c.308A>T	p.His103Leu	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RP9	ENST00000297157.8	c.410A>T	p.His137Leu	missense_variant	5/6	1	NM_203288.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Retinitis pigmentosa 9 Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Jul 01, 2006

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.38	T;.
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.92	D;D
MetaSVM	Uncertain	-0.071	T
MutationAssessor	Benign	2.0	M;.
MutationTaster	Benign	1.0	A
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-9.9	D;D
REVEL	Pathogenic	0.73
Sift	Uncertain	0.026	D;D
Sift4G	Benign	0.069	T;.
Polyphen		0.80	P;.
Vest4		0.95
MutPred		0.77		Loss of helix (P = 0.0558);.;
MVP		0.90
MPC		1.1
ClinPred		0.99	D
GERP RS		3.5
Varity_R		0.60
gMVP		0.23

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: rs104894037; hg19: chr7-33136162;