5-178149487-C-T

Variant summary

Our verdict is Benign. Variant got -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

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 1699894.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NHP2	NM_017838.4	c.*226G>A		3_prime_UTR_variant	4/4	ENST00000274606.8
RMND5B	NM_022762.5	c.*1455C>T		3_prime_UTR_variant	11/11	ENST00000313386.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NHP2	ENST00000274606.8	c.*226G>A		3_prime_UTR_variant	4/4	1	NM_017838.4	P1
RMND5B	ENST00000313386.9	c.*1455C>T		3_prime_UTR_variant	11/11	1	NM_022762.5	P1

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

Gnomad4 AFR exome AF: 0.0126

Gnomad4 AMR exome AF: 0.00103

Gnomad4 ASJ exome AF: 0.00109

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000454

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000525

Gnomad4 OTH exome AF: 0.000936

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

Gnomad4 AFR AF: 0.0116

Gnomad4 AMR AF: 0.000849

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.0000697 Hom.: 0

Bravo AF: 0.00378

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 13, 2020

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	8.9
Dann	Benign	0.66

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

Other links and lift over

dbSNP: rs142189994; hg19: chr5-177576488;