NM_014014.5:c.*101A>G

Variant names:

• chr2-96274911-T-C
• rs184527047
• NM_014014.5:c.*101A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014014.5(SNRNP200):​c.*101A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0025 in 1,418,568 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (6 hom.)
• Consequence: SNRNP200 NM_014014.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.495
• Publications: 0 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-96274911-T-C is Benign according to our data. Variant chr2-96274911-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 337521.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00182 (277/152298) while in subpopulation NFE AF = 0.00303 (206/68026). AF 95% confidence interval is 0.00269. There are 0 homozygotes in GnomAd4. There are 154 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 277 AD gene.

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.*101A>G		3_prime_UTR	Exon 45 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.*101A>G		3_prime_UTR	Exon 45 of 45	ENSP00000317123.5	O75643-1
	SNRNP200	ENST00000497539.5	TSL:1	n.2486A>G		non_coding_transcript_exon	Exon 15 of 15
	SNRNP200	ENST00000914240.1		c.*101A>G		3_prime_UTR	Exon 45 of 45	ENSP00000584299.1

Frequencies

GnomAD3 genomes AF: 0.00182 AC: 277 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00303

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.00258 AC: 3268 AN: 1266270 Hom.: 6 Cov.: 18 AF XY: 0.00251 AC XY: 1608 AN XY: 639960

African (AFR) AF: 0.000370 AC: 11 AN: 29768

American (AMR) AF: 0.000337 AC: 15 AN: 44456

Ashkenazi Jewish (ASJ) AF: 0.00180 AC: 45 AN: 24938

East Asian (EAS) AF: 0.00 AC: 0 AN: 38738

South Asian (SAS) AF: 0.00 AC: 0 AN: 81860

European-Finnish (FIN) AF: 0.00378 AC: 180 AN: 47576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3752

European-Non Finnish (NFE) AF: 0.00312 AC: 2938 AN: 941222

Other (OTH) AF: 0.00146 AC: 79 AN: 53960

GnomAD4 genome AF: 0.00182 AC: 277 AN: 152298 Hom.: 0 Cov.: 33 AF XY: 0.00207 AC XY: 154 AN XY: 74476

African (AFR) AF: 0.000361 AC: 15 AN: 41558

American (AMR) AF: 0.000719 AC: 11 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00339 AC: 36 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00303 AC: 206 AN: 68026

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00286 Hom.: 1

Bravo AF: 0.00137

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.52
PhyloP100		-0.49
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.2
Mutation Taster		=100/0	polymorphism

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: rs184527047; hg19: chr2-96940649;