2-96274681-C-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_014014.5(SNRNP200):​c.*331G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000854 in 374,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00093 ( 0 hom. )

Consequence

SNRNP200
NM_014014.5 3_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.50
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000742 (113/152308) while in subpopulation AMR AF= 0.000915 (14/15302). AF 95% confidence interval is 0.000716. There are 0 homozygotes in gnomad4. There are 43 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High AC in GnomAd4 at 113 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SNRNP200NM_014014.5 linkuse as main transcriptc.*331G>C 3_prime_UTR_variant 45/45 ENST00000323853.10 NP_054733.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SNRNP200ENST00000323853.10 linkuse as main transcriptc.*331G>C 3_prime_UTR_variant 45/451 NM_014014.5 ENSP00000317123 P1O75643-1
SNRNP200ENST00000497539.5 linkuse as main transcript downstream_gene_variant 1

Frequencies

GnomAD3 genomes
AF:
0.000742
AC:
113
AN:
152190
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000916
Gnomad ASJ
AF:
0.00720
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000897
Gnomad OTH
AF:
0.000478
GnomAD4 exome
AF:
0.000930
AC:
207
AN:
222520
Hom.:
0
Cov.:
0
AF XY:
0.000963
AC XY:
116
AN XY:
120484
show subpopulations
Gnomad4 AFR exome
AF:
0.000155
Gnomad4 AMR exome
AF:
0.000803
Gnomad4 ASJ exome
AF:
0.00731
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000438
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000915
Gnomad4 OTH exome
AF:
0.00139
GnomAD4 genome
AF:
0.000742
AC:
113
AN:
152308
Hom.:
0
Cov.:
33
AF XY:
0.000577
AC XY:
43
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.000915
Gnomad4 ASJ
AF:
0.00720
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000897
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000902
Hom.:
0
Bravo
AF:
0.000869
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

Retinitis pigmentosa Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
4.7
DANN
Benign
0.49

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs557818805; hg19: chr2-96940419; API