chr4-122917602-C-T

Variant summary

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

The NM_007083.5(NUDT6):​c.341G>A​(p.Cys114Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,878 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. 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. C114F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

NUDT6
NM_007083.5 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.688
Variant links:
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]

Genome browser will be placed here

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=0.14871025).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NUDT6NM_007083.5 linkc.341G>A p.Cys114Tyr missense_variant Exon 2 of 5 ENST00000304430.10 NP_009014.2 P53370-1
NUDT6NM_198041.3 linkc.-167G>A 5_prime_UTR_variant Exon 2 of 5 NP_932158.1 P53370-2B4DG76

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NUDT6ENST00000304430.10 linkc.341G>A p.Cys114Tyr missense_variant Exon 2 of 5 1 NM_007083.5 ENSP00000306070.5 P53370-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461878
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
15
DANN
Benign
0.44
DEOGEN2
Benign
0.067
T
Eigen
Benign
-0.95
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.059
N
LIST_S2
Benign
0.20
T
M_CAP
Benign
0.0080
T
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.75
N
REVEL
Benign
0.082
Sift
Benign
0.059
T
Sift4G
Uncertain
0.041
D
Polyphen
0.68
P
Vest4
0.075
MVP
0.13
MPC
0.19
ClinPred
0.11
T
GERP RS
2.0
Varity_R
0.12
gMVP
0.71

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.

Other links and lift over

dbSNP: rs1469563599; hg19: chr4-123838757; COSMIC: COSV58647563; COSMIC: COSV58647563; API