chr4-122922518-C-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_007083.5(NUDT6):c.55G>C(p.Gly19Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 1,608,402 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.012 ( 40 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 32 hom. )
Consequence
NUDT6
NM_007083.5 missense
NM_007083.5 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: -2.08
Genes affected
NUDT6 (HGNC:8053): (nudix hydrolase 6) This gene overlaps and lies on the opposite strand from FGF2 gene, and is thought to be the FGF2 antisense gene. The two genes are independently transcribed, and their expression shows an inverse relationship, suggesting that this antisense transcript may regulate FGF2 expression. This gene has also been shown to have hormone-regulatory and antiproliferative actions in the pituitary that are independent of FGF2 expression. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.00213027).
BP6
?
Variant 4-122922518-C-G is Benign according to our data. Variant chr4-122922518-C-G is described in ClinVar as [Benign]. Clinvar id is 3037688.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.012 (1831/152332) while in subpopulation AFR AF= 0.0409 (1701/41582). AF 95% confidence interval is 0.0393. There are 40 homozygotes in gnomad4. There are 857 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 40 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NUDT6 | NM_007083.5 | c.55G>C | p.Gly19Arg | missense_variant | 1/5 | ENST00000304430.10 | |
NUDT6 | NM_198041.3 | c.-270+283G>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NUDT6 | ENST00000304430.10 | c.55G>C | p.Gly19Arg | missense_variant | 1/5 | 1 | NM_007083.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0120 AC: 1825AN: 152214Hom.: 40 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00378 AC: 886AN: 234242Hom.: 18 AF XY: 0.00293 AC XY: 379AN XY: 129238
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GnomAD4 exome AF: 0.00143 AC: 2077AN: 1456070Hom.: 32 Cov.: 29 AF XY: 0.00124 AC XY: 896AN XY: 724500
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GnomAD4 genome ? AF: 0.0120 AC: 1831AN: 152332Hom.: 40 Cov.: 32 AF XY: 0.0115 AC XY: 857AN XY: 74492
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ESP6500AA
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148
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487
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
NUDT6-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 06, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
M
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
D
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at