7-33095371-T-C

Variant summary

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

The NM_203288.2(RP9):c.529A>G(p.Ser177Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RP9 NM_203288.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.941

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]

LOC124901610 (HGNC:):

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=0.17058894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RP9	NM_203288.2	c.529A>G	p.Ser177Gly	missense_variant	6/6	ENST00000297157.8
LOC124901610	XR_007060277.1	n.1298T>C		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RP9	ENST00000297157.8	c.529A>G	p.Ser177Gly	missense_variant	6/6	1	NM_203288.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 24, 2023

The c.529A>G (p.S177G) alteration is located in exon 6 (coding exon 6) of the RP9 gene. This alteration results from a A to G substitution at nucleotide position 529, causing the serine (S) at amino acid position 177 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
Cadd	Benign	21
Dann	Benign	0.97
DEOGEN2	Benign	0.36	T;.
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	0.55	D
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.14
Sift	Uncertain	0.020	D;D
Sift4G	Benign	0.14	T;.
Polyphen		0.22	B;.
Vest4		0.17
MutPred		0.20		Loss of phosphorylation at S177 (P = 6e-04);.;
MVP		0.73
MPC		0.83
ClinPred		0.56	D
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.093
gMVP		0.019

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: chr7-33134983;