11-64229288-G-C

Position:

• chr11-64229288-G-C

Variant summary

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

The NM_032344.4(NUDT22):​c.621G>C​(p.Leu207Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NUDT22 NM_032344.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.84

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]

ENSG00000256116 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUDT22	NM_032344.4	c.621G>C	p.Leu207Phe	missense_variant	4/6	ENST00000279206.8	NP_115720.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUDT22	ENST00000279206.8	c.621G>C	p.Leu207Phe	missense_variant	4/6	1	NM_032344.4	ENSP00000279206.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Apr 14, 2022

The c.621G>C (p.L207F) alteration is located in exon 4 (coding exon 3) of the NUDT22 gene. This alteration results from a G to C substitution at nucleotide position 621, causing the leucine (L) at amino acid position 207 to be replaced by a phenylalanine (F). 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	Uncertain	0.50
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	.;T;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.82	T;D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.5	.;M;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.4	N;D;D
REVEL	Benign	0.19
Sift	Uncertain	0.011	D;D;D
Sift4G	Benign	0.067	T;D;T
Polyphen		1.0	.;D;.
Vest4		0.61
MutPred		0.37		.;Loss of methylation at R211 (P = 0.1768);.;
MVP		0.44
MPC		1.3
ClinPred		0.96	D
GERP RS		4.0
Varity_R		0.45
gMVP		0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-63996760;