rs1253288868

Variant names:

• chr10-12172848-C-G
• rs1253288868
• NM_014142.4:c.404G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-12172848-C-G
• chr10-12172848-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_014142.4(NUDT5):​c.404G>C​(p.Gly135Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G135D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NUDT5 NM_014142.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.17
• Publications: 0 publications found

Genes affected

NUDT5 (HGNC:8052): (nudix hydrolase 5) This gene belongs to the Nudix (nucleoside diphosphate linked moiety X) hydrolase superfamily. The encoded enzyme catalyzes the hydrolysis of modified nucleoside diphosphates, including ADP-ribose (ADPR) and 8-oxoGua-containing 8-oxo-dADP and 8-oxo-dGDP. Protein-bound ADP ribose can be hazardous to the cell because it can modify some amino acid residues, resulting in the inhibition of ATP-activated potassium channels. 8-oxoGua is an oxidized form of guanine that can potentially alter genetic information by pairing with adenine and cytosine in RNA. Presence of 8-oxoGua in RNA results in formation of abnormal proteins due to translational errors. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.986

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014142.4. 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
	NUDT5	NM_014142.4	MANE Select	c.404G>C	p.Gly135Ala	missense	Exon 7 of 10	NP_054861.2
	NUDT5	NM_001321647.2		c.404G>C	p.Gly135Ala	missense	Exon 7 of 9	NP_001308576.1
	NUDT5	NM_001321648.2		c.146G>C	p.Gly49Ala	missense	Exon 8 of 11	NP_001308577.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT5	ENST00000491614.6	TSL:1 MANE Select	c.404G>C	p.Gly135Ala	missense	Exon 7 of 10	ENSP00000419628.1	Q9UKK9
	NUDT5	ENST00000378937.7	TSL:3	c.443G>C	p.Gly148Ala	missense	Exon 8 of 11	ENSP00000368219.3	A6NFX8
	NUDT5	ENST00000905393.1		c.404G>C	p.Gly135Ala	missense	Exon 7 of 10	ENSP00000575452.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461754 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727188

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111910

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.053	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.9	M
PhyloP100		6.2
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.54
Sift	Uncertain	0.022	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.92		Loss of sheet (P = 0.0817)
MVP		0.85
MPC		1.0
ClinPred		0.98	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.79
gMVP		0.82
Mutation Taster		=21/79	disease causing

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: rs1253288868; hg19: chr10-12214847;