NM_015412.4:c.1529G>A

Variant names:

• chr3-113005711-C-T
• rs1363944298
• NM_015412.4:c.1529G>A

Variant summary

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

The NM_015412.4(RMP64):​c.1529G>A​(p.Gly510Glu) 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. 14/20 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. G510V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RMP64 NM_015412.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.323
• Publications: 0 publications found

Genes affected

RMP64 (HGNC:24496): (nucleolus and neural progenitor protein) Predicted to be involved in negative regulation of neuron differentiation and positive regulation of Notch signaling pathway. Predicted to be located in nucleolus. Predicted to be active in nucleus. Implicated in anauxetic dysplasia 3. [provided by Alliance of Genome Resources, Apr 2022]

GTPBP8 (HGNC:25007): (GTP binding protein 8 (putative)) Predicted to enable GTP binding activity and metal ion binding activity. Located in mitochondrion. [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=0.06353682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RMP64	NM_015412.4	c.1529G>A	p.Gly510Glu	missense_variant	Exon 9 of 9	ENST00000314400.10	NP_056227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEPRO	ENST00000314400.10	c.1529G>A	p.Gly510Glu	missense_variant	Exon 9 of 9	1	NM_015412.4	ENSP00000320251.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.8
DANN	Benign	0.73
DEOGEN2	Benign	0.0017	T;.
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.064	T;T
MetaSVM	Benign	-1.1	T
PhyloP100		0.32
PROVEAN	Benign	-0.20	N;N
REVEL	Benign	0.0080
Sift	Benign	0.41	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.26	B;B
Vest4		0.063
MutPred		0.31		Gain of solvent accessibility (P = 0.0456);.;
MVP		0.27
MPC		0.21
ClinPred		0.068	T
GERP RS		1.4
Varity_R		0.046
gMVP		0.032
Mutation Taster		=95/5	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: rs1363944298; hg19: chr3-112724558;