8-22108279-C-G

Variant names:

• chr8-22108279-C-G
• NM_024815.4:c.230G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024815.4(NUDT18):​c.230G>C​(p.Arg77Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NUDT18 NM_024815.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.50

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.792

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT18	NM_024815.4	c.230G>C	p.Arg77Thr	missense_variant	Exon 2 of 3	ENST00000611621.2	NP_079091.3
NUDT18	XM_011544650.2	c.878G>C	p.Arg293Thr	missense_variant	Exon 3 of 4		XP_011542952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDT18	ENST00000611621.2	c.230G>C	p.Arg77Thr	missense_variant	Exon 2 of 3	1	NM_024815.4	ENSP00000480722.1
NUDT18	ENST00000613958.1	c.230G>C	p.Arg77Thr	missense_variant	Exon 2 of 2	2		ENSP00000479883.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 11, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.230G>C (p.R77T) alteration is located in exon 2 (coding exon 2) of the NUDT18 gene. This alteration results from a G to C substitution at nucleotide position 230, causing the arginine (R) at amino acid position 77 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Benign	0.76	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Benign	0.0083	T
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Uncertain	0.71	T
Sift4G	Uncertain	0.0060	D;T
Polyphen		1.0	D;.
Vest4		0.93
MutPred		0.52		Gain of glycosylation at R77 (P = 0.0142);Gain of glycosylation at R77 (P = 0.0142);
MVP		0.51
ClinPred		0.96	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.87
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-21965790;