chr8-22109276-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024815.4(NUDT18):​c.25G>A​(p.Ala9Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000243 in 1,396,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: NUDT18 NM_024815.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0063221455).

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>A	p.Ala9Thr	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>A	p.Ala9Thr	missense	Exon 1 of 3	ENSP00000480722.1	Q6ZVK8-1
	NUDT18	ENST00000613958.2	TSL:2	c.25G>A	p.Ala9Thr	missense	Exon 1 of 2	ENSP00000479883.1	A0A087WW30

Frequencies

GnomAD3 genomes AF: 0.00139 AC: 211 AN: 151874 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00481

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000175 AC: 6 AN: 34314 AF XY: 0.00

Gnomad AFR exome AF: 0.0127

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000103 AC: 128 AN: 1244652 Hom.: 0 Cov.: 32 AF XY: 0.0000820 AC XY: 50 AN XY: 609906

African (AFR) AF: 0.00441 AC: 108 AN: 24470

American (AMR) AF: 0.000331 AC: 5 AN: 15102

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19708

East Asian (EAS) AF: 0.00 AC: 0 AN: 27160

South Asian (SAS) AF: 0.0000336 AC: 2 AN: 59564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3650

European-Non Finnish (NFE) AF: 9.87e-7 AC: 1 AN: 1013132

Other (OTH) AF: 0.000235 AC: 12 AN: 51062

GnomAD4 genome AF: 0.00139 AC: 211 AN: 151980 Hom.: 0 Cov.: 34 AF XY: 0.00136 AC XY: 101 AN XY: 74334

African (AFR) AF: 0.00480 AC: 199 AN: 41450

American (AMR) AF: 0.000458 AC: 7 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67922

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.0000713 Hom.: 0

Bravo AF: 0.00137

Asia WGS AF: 0.000290 AC: 1 AN: 3460

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.47	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.0063	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.53
PrimateAI	Benign	0.45	T
Sift4G	Benign	0.19	T
Polyphen		0.0010	B
Vest4		0.030
MutPred		0.33		Loss of helix (P = 0.0017)
MVP		0.095
ClinPred		0.033	T
GERP RS		2.3
PromoterAI		0.0025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.039
gMVP		0.34
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; COSMIC: COSV105864351; COSMIC: COSV105864351;