chr2-96275109-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate

The NM_014014.5(SNRNP200):​c.6314C>T​(p.Thr2105Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SNRNP200
NM_014014.5 missense

Scores

9
6
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.66
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SNRNP200. . Gene score misZ: 5.9363 (greater than the threshold 3.09). Trascript score misZ: 8.7488 (greater than threshold 3.09). The gene has 14 curated pathogenic missense variants (we use a threshold of 10). The gene has 26 curated benign missense variants. GenCC has associacion of the gene with retinitis pigmentosa 33, SNRNP200-related dominant retinopathy, retinitis pigmentosa.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.913

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SNRNP200NM_014014.5 linkc.6314C>T p.Thr2105Ile missense_variant 45/45 ENST00000323853.10 NP_054733.2 O75643-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SNRNP200ENST00000323853.10 linkc.6314C>T p.Thr2105Ile missense_variant 45/451 NM_014014.5 ENSP00000317123.5 O75643-1
SNRNP200ENST00000497539.5 linkn.2288C>T non_coding_transcript_exon_variant 15/151
SNRNP200ENST00000429650.1 linkn.2545C>T non_coding_transcript_exon_variant 17/172

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461880
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727242
show subpopulations
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.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 27, 2022The c.6314C>T (p.T2105I) alteration is located in exon 45 (coding exon 45) of the SNRNP200 gene. This alteration results from a C to T substitution at nucleotide position 6314, causing the threonine (T) at amino acid position 2105 to be replaced by an isoleucine (I). 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
0.16
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.21
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.39
T
Eigen
Pathogenic
0.93
Eigen_PC
Pathogenic
0.85
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Pathogenic
0.44
D
MetaRNN
Pathogenic
0.91
D
MetaSVM
Uncertain
0.39
D
MutationAssessor
Pathogenic
3.3
M
PrimateAI
Pathogenic
0.91
D
PROVEAN
Uncertain
-2.8
D
REVEL
Uncertain
0.59
Sift
Benign
0.035
D
Sift4G
Uncertain
0.027
D
Polyphen
0.98
D
Vest4
0.83
MutPred
0.58
Loss of catalytic residue at F2108 (P = 0.1231);
MVP
0.54
MPC
1.8
ClinPred
0.96
D
GERP RS
5.4
Varity_R
0.56
gMVP
0.80

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: chr2-96940847; API