rs104894037

Variant names:

• chr7-33096550-T-A
• rs104894037
• NM_203288.2:c.410A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-33096550-T-A
• chr7-33096550-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 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 (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RP9 NM_203288.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 6.15
• Publications: 17 publications found

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]

RP9 Gene-Disease associations (from GenCC):

• retinitis pigmentosa 9

  Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: ClinGen, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203288.2. 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
	RP9	NM_203288.2	MANE Select	c.410A>T	p.His137Leu	missense	Exon 5 of 6	NP_976033.1	Q8TA86

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RP9	ENST00000297157.8	TSL:1 MANE Select	c.410A>T	p.His137Leu	missense	Exon 5 of 6	ENSP00000297157.3	Q8TA86
	RP9	ENST00000448915.1	TSL:3	c.308A>T	p.His103Leu	missense	Exon 5 of 6	ENSP00000411577.1	C9J6V2
	RP9	ENST00000684207.1		c.410A>T	p.His137Leu	missense	Exon 5 of 5	ENSP00000506942.1	A0A804HI79

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	Retinitis pigmentosa 9 (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	-0.071	T
MutationAssessor	Benign	2.0	M
PhyloP100		6.2
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-9.9	D
REVEL	Pathogenic	0.73
Sift	Uncertain	0.026	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
Mutation Taster		=50/50

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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: rs104894037; hg19: chr7-33136162;