Variant chr11-64226692-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032344.4(NUDT22):c.40G>A(p.Gly14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,456,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G14E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

NUDT22
NM_032344.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

Variant links:

Genes affected

NUDT22 (HGNC:28189): (nudix hydrolase 22) Enables UDP-sugar diphosphatase activity and metal ion binding activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NUDT22 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18236798).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUDT22	NM_032344.4 linkuse as main transcript	c.40G>A	p.Gly14Arg	missense_variant	2/6	ENST00000279206.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUDT22	ENST00000279206.8 linkuse as main transcript	c.40G>A	p.Gly14Arg	missense_variant	2/6	1	NM_032344.4	P1	Q9BRQ3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1456022

Hom.:

Cov.:

AF XY:

0.00000828

AC XY:

AN XY:

724322

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2024

The c.40G>A (p.G14R) alteration is located in exon 2 (coding exon 1) of the NUDT22 gene. This alteration results from a G to A substitution at nucleotide position 40, causing the glycine (G) at amino acid position 14 to be replaced by an arginine (R). 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

Benign

0.13

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.051

T;.;T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.80

T;T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.18

T;T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.7

N;N;N;N

REVEL

Benign

0.023

Sift

Benign

0.11

T;D;D;D

Sift4G

Benign

0.65

T;T;T;T

Polyphen

0.62

.;.;P;.

Vest4

0.28, 0.24

MutPred

0.26

Gain of solvent accessibility (P = 0.0014);Gain of solvent accessibility (P = 0.0014);Gain of solvent accessibility (P = 0.0014);Gain of solvent accessibility (P = 0.0014);

MVP

0.49

MPC

0.52

ClinPred

0.34

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.13

gMVP

0.50

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over