8-22109276-C-G

Variant names:

• chr8-22109276-C-G
• rs536801022
• NM_024815.4:c.25G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024815.4(NUDT18):​c.25G>C​(p.Ala9Pro) 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. 11/17 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. A9T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: NUDT18 NM_024815.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.530
• Publications: 0 publications found

Genes affected

NUDT18 (HGNC:26194): (nudix hydrolase 18) The protein encoded by this gene is a member of the Nudix hydrolase family. Nudix hydrolases eliminate potentially toxic nucleotide metabolites from the cell and regulate the concentrations and availability of many different nucleotide substrates, cofactors, and signaling molecules. This protein contains a Nudix hydrolase domain and hydrolyzes oxidized forms of guanosine and deoxyguanosine diphosphates. [provided by RefSeq, Sep 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13654688).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024815.4. 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
	NUDT18	NM_024815.4	MANE Select	c.25G>C	p.Ala9Pro	missense	Exon 1 of 3	NP_079091.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT18	ENST00000611621.2	TSL:1 MANE Select	c.25G>C	p.Ala9Pro	missense	Exon 1 of 3	ENSP00000480722.1	Q6ZVK8-1
	NUDT18	ENST00000613958.2	TSL:2	c.25G>C	p.Ala9Pro	missense	Exon 1 of 2	ENSP00000479883.1	A0A087WW30

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.52	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.53
PrimateAI	Benign	0.48	T
Sift4G	Benign	0.15	T
Polyphen		0.61	P
Vest4		0.19
MutPred		0.42		Loss of helix (P = 3e-04)
MVP		0.15
ClinPred		0.81	D
GERP RS		2.3
PromoterAI		-0.041	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.20
gMVP		0.49
Mutation Taster		=99/1	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: rs536801022; hg19: chr8-21966789;