NM_022762.5:c.*1455C>T

Variant names:

• chr5-178149487-C-T
• rs142189994
• NM_022762.5:c.*1455C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_022762.5(RMND5B):​c.*1455C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 540,018 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00050 (1 hom.)
• Consequence: RMND5B NM_022762.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0820
• Publications: 0 publications found

Genes affected

RMND5B (HGNC:26181): (required for meiotic nuclear division 5 homolog B) Predicted to enable metal ion binding activity and ubiquitin protein ligase activity. Predicted to contribute to ubiquitin-protein transferase activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

NHP2 (HGNC:14377): (NHP2 ribonucleoprotein) This gene is a member of the H/ACA snoRNPs (small nucleolar ribonucleoproteins) gene family. snoRNPs are involved in various aspects of rRNA processing and modification and have been classified into two families: C/D and H/ACA. The H/ACA snoRNPs also include the DKC1, NOLA1 and NOLA3 proteins. These four H/ACA snoRNP proteins localize to the dense fibrillar components of nucleoli and to coiled (Cajal) bodies in the nucleus. Both 18S rRNA production and rRNA pseudouridylation are impaired if any one of the four proteins is depleted. The four H/ACA snoRNP proteins are also components of the telomerase complex. This gene encodes a protein related to Saccharomyces cerevisiae Nhp2p. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2008]

NHP2 Gene-Disease associations (from GenCC):

• dyskeratosis congenita, autosomal recessive 2

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• dyskeratosis congenita

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 5-178149487-C-T is Benign according to our data. Variant chr5-178149487-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1699894.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022762.5. 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
	RMND5B	NM_022762.5	MANE Select	c.*1455C>T		3_prime_UTR	Exon 11 of 11	NP_073599.2
	NHP2	NM_017838.4	MANE Select	c.*226G>A		3_prime_UTR	Exon 4 of 4	NP_060308.1	Q9NX24
	RMND5B	NM_001288794.2		c.*1455C>T		3_prime_UTR	Exon 12 of 12	NP_001275723.1	Q96G75-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMND5B	ENST00000313386.9	TSL:1 MANE Select	c.*1455C>T		3_prime_UTR	Exon 11 of 11	ENSP00000320623.4	Q96G75-1
	NHP2	ENST00000274606.8	TSL:1 MANE Select	c.*226G>A		3_prime_UTR	Exon 4 of 4	ENSP00000274606.4	Q9NX24
	RMND5B	ENST00000940697.1		c.*1455C>T		3_prime_UTR	Exon 11 of 11	ENSP00000610756.1

Frequencies

GnomAD3 genomes AF: 0.00330 AC: 503 AN: 152236 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.000503 AC: 195 AN: 387664 Hom.: 1 Cov.: 5 AF XY: 0.000369 AC XY: 75 AN XY: 203202

African (AFR) AF: 0.0126 AC: 133 AN: 10586

American (AMR) AF: 0.00103 AC: 16 AN: 15502

Ashkenazi Jewish (ASJ) AF: 0.00109 AC: 12 AN: 11036

East Asian (EAS) AF: 0.00 AC: 0 AN: 23378

South Asian (SAS) AF: 0.0000454 AC: 2 AN: 44084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1572

European-Non Finnish (NFE) AF: 0.0000525 AC: 12 AN: 228516

Other (OTH) AF: 0.000936 AC: 20 AN: 21362

GnomAD4 genome AF: 0.00331 AC: 505 AN: 152354 Hom.: 2 Cov.: 33 AF XY: 0.00298 AC XY: 222 AN XY: 74504

African (AFR) AF: 0.0116 AC: 482 AN: 41576

American (AMR) AF: 0.000849 AC: 13 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.0000697 Hom.: 0

Bravo AF: 0.00378

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.9
DANN	Benign	0.66
PhyloP100		0.082
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: rs142189994; hg19: chr5-177576488;