chr11-64226941-A-G

Position:

• chr11-64226941-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032344.4(NUDT22):​c.289A>G​(p.Ser97Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: NUDT22 NM_032344.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.709

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 (HGNC:):

ACMG classification

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=0.08430821).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUDT22	NM_032344.4	c.289A>G	p.Ser97Gly	missense_variant	2/6	ENST00000279206.8	NP_115720.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUDT22	ENST00000279206.8	c.289A>G	p.Ser97Gly	missense_variant	2/6	1	NM_032344.4	ENSP00000279206.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2021

The c.289A>G (p.S97G) alteration is located in exon 2 (coding exon 1) of the NUDT22 gene. This alteration results from a A to G substitution at nucleotide position 289, causing the serine (S) at amino acid position 97 to be replaced by a glycine (G). 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	0.063
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.017	T;.;T;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.34	T;T;T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.084	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	.;L;L;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.82	N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.60	T;T;T;T
Sift4G	Benign	0.51	T;T;T;T
Polyphen		0.0020	.;.;B;.
Vest4		0.21, 0.11
MutPred		0.32		Loss of MoRF binding (P = 0.1743);Loss of MoRF binding (P = 0.1743);Loss of MoRF binding (P = 0.1743);Loss of MoRF binding (P = 0.1743);
MVP		0.43
MPC		0.36
ClinPred		0.051	T
GERP RS		4.5
Varity_R		0.18
gMVP		0.46

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

Other links and lift over

dbSNP: rs1438890593; hg19: chr11-63994413;