rs397514575

Variant names:

• chr2-96290415-G-C
• rs397514575
• NM_014014.5:c.2653C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_014014.5(SNRNP200):​c.2653C>G​(p.Gln885Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. Q885Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNRNP200 NM_014014.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 10.0
• Publications: 6 publications found

Genes affected

SNRNP200 (HGNC:30859): (small nuclear ribonucleoprotein U5 subunit 200) Pre-mRNA splicing is catalyzed by the spliceosome, a complex of specialized RNA and protein subunits that removes introns from a transcribed pre-mRNA segment. The spliceosome consists of small nuclear RNA proteins (snRNPs) U1, U2, U4, U5 and U6, together with approximately 80 conserved proteins. U5 snRNP contains nine specific proteins. This gene encodes one of the U5 snRNP-specific proteins. This protein belongs to the DEXH-box family of putative RNA helicases. It is a core component of U4/U6-U5 snRNPs and appears to catalyze an ATP-dependent unwinding of U4/U6 RNA duplices. Mutations in this gene cause autosomal-dominant retinitis pigmentosa. Alternatively spliced transcript variants encoding different isoforms have been found, but the full-length nature of these variants has not been determined. [provided by RefSeq, Mar 2010]

SNRNP200 Gene-Disease associations (from GenCC):

• SNRNP200-related dominant retinopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 33

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-96290415-G-C is Pathogenic according to our data. Variant chr2-96290415-G-C is described in ClinVar as Pathogenic. ClinVar VariationId is 39747.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014014.5. 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
	SNRNP200	NM_014014.5	MANE Select	c.2653C>G	p.Gln885Glu	missense	Exon 20 of 45	NP_054733.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRNP200	ENST00000323853.10	TSL:1 MANE Select	c.2653C>G	p.Gln885Glu	missense	Exon 20 of 45	ENSP00000317123.5	O75643-1
	SNRNP200	ENST00000914240.1		c.2686C>G	p.Gln896Glu	missense	Exon 20 of 45	ENSP00000584299.1
	SNRNP200	ENST00000960227.1		c.2653C>G	p.Gln885Glu	missense	Exon 20 of 45	ENSP00000630286.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Retinitis pigmentosa 33 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.098	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	0.47	N
PhyloP100		10
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.48
Sift	Benign	0.075	T
Sift4G	Benign	0.069	T
Polyphen		0.24	B
Vest4		0.88
MutPred		0.40		Gain of helix (P = 0.0496)
MVP		0.89
MPC		1.1
ClinPred		0.64	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.84
Mutation Taster		=19/81	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs397514575; hg19: chr2-96956153;