8-22107858-C-A

Variant names:

• chr8-22107858-C-A
• NM_024815.4:c.414G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024815.4(NUDT18):​c.414G>T​(p.Glu138Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.782

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDT18	NM_024815.4	c.414G>T	p.Glu138Asp	missense_variant	Exon 3 of 3	ENST00000611621.2	NP_079091.3
NUDT18	XM_011544650.2	c.1062G>T	p.Glu354Asp	missense_variant	Exon 4 of 4		XP_011542952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDT18	ENST00000611621.2	c.414G>T	p.Glu138Asp	missense_variant	Exon 3 of 3	1	NM_024815.4	ENSP00000480722.1
NUDT18	ENST00000613958	c.*249G>T		3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000479883.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.414G>T (p.E138D) alteration is located in exon 3 (coding exon 3) of the NUDT18 gene. This alteration results from a G to T substitution at nucleotide position 414, causing the glutamic acid (E) at amino acid position 138 to be replaced by an aspartic acid (D). 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	Uncertain	0.56
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.57	T
Sift4G	Benign	0.084	T
Polyphen		0.97	D
Vest4		0.60
MutPred		0.75		Gain of helix (P = 0.1736);
MVP		0.35
ClinPred		0.88	D
GERP RS		4.5
Varity_R		0.69
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr8-21965369;