Genetic Variant NUDT12:p.Leu275Val (chr5-103556072-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_031438.4(NUDT12):c.823C>G(p.Leu275Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,218 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L275F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NUDT12
NM_031438.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.15

Publications

0 publications found

Variant links:

Genes affected

NUDT12 (HGNC:18826): (nudix hydrolase 12) Nucleotides are involved in numerous biochemical reactions and pathways within the cell as substrates, cofactors, and effectors. Nudix hydrolases, such as NUDT12, regulate the concentrations of individual nucleotides and of nucleotide ratios in response to changing circumstances (Abdelraheim et al., 2003 [PubMed 12790796]).[supplied by OMIM, Mar 2008]

NUDT12 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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
NUDT12	NM_031438.4 link	c.823C>G	p.Leu275Val	missense_variant	Exon 4 of 7	ENST00000230792.7	NP_113626.1	Q9BQG2-1
NUDT12	NM_001300741.2 link	c.769C>G	p.Leu257Val	missense_variant	Exon 4 of 7		NP_001287670.1	Q9BQG2-2
NUDT12	XM_005272095.2 link	c.823C>G	p.Leu275Val	missense_variant	Exon 4 of 7		XP_005272152.1	Q9BQG2-1
NUDT12	XM_005272097.4 link	c.769C>G	p.Leu257Val	missense_variant	Exon 4 of 7		XP_005272154.1	Q9BQG2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NUDT12	ENST00000230792.7 link	c.823C>G	p.Leu275Val	missense_variant	Exon 4 of 7	1	NM_031438.4	ENSP00000230792.2	Q9BQG2-1
NUDT12	ENST00000507423.1 link	c.769C>G	p.Leu257Val	missense_variant	Exon 4 of 7	2		ENSP00000424521.1	Q9BQG2-2
NUDT12	ENST00000515407.1 link	n.18C>G		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1457218

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724810

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33266

American (AMR)

AF:

0.00

AC:

AN:

44254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25910

East Asian (EAS)

AF:

0.0000758

AC:

AN:

39590

South Asian (SAS)

AF:

0.00

AC:

AN:

85298

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53286

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109716

Other (OTH)

AF:

0.00

AC:

AN:

60148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

T;.

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.51

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

M;.

PhyloP100

3.2

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.010

D;D

Sift4G

Benign

0.18

T;T

Polyphen

0.070

B;P

Vest4

0.65

MutPred

0.67

Loss of helix (P = 0.0444);.;

MVP

0.49

MPC

0.083

ClinPred

0.92

GERP RS

5.3

Varity_R

0.25

gMVP

0.66

Mutation Taster

=54/46

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over