5-178149824-G-T

Variant names:

• chr5-178149824-G-T
• NM_017838.4:c.351C>A
• NHP2 p.Ala117Ala

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001396110.1(NHP2):​c.479C>A​(p.Pro160Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P160L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NHP2 NM_001396110.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.70
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052200913).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001396110.1. 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
	NHP2	NM_017838.4	MANE Select	c.351C>A	p.Ala117Ala	synonymous	Exon 4 of 4	NP_060308.1	Q9NX24
	RMND5B	NM_022762.5	MANE Select	c.*1792G>T		3_prime_UTR	Exon 11 of 11	NP_073599.2
	NHP2	NM_001396110.1		c.479C>A	p.Pro160Gln	missense	Exon 5 of 5	NP_001383039.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHP2	ENST00000274606.8	TSL:1 MANE Select	c.351C>A	p.Ala117Ala	synonymous	Exon 4 of 4	ENSP00000274606.4	Q9NX24
	RMND5B	ENST00000313386.9	TSL:1 MANE Select	c.*1792G>T		3_prime_UTR	Exon 11 of 11	ENSP00000320623.4	Q96G75-1
	NHP2	ENST00000314397.9	TSL:2	c.245C>A	p.Pro82Gln	missense	Exon 3 of 3	ENSP00000366276.2	J3QSY4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.082
DANN	Benign	0.81
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.96	T
PhyloP100		-3.7
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.10
Sift	Benign	0.068	T
Sift4G	Benign	0.079	T
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-177576825;