chr14-77405934-C-T

Variant summary

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

The NM_001113475.3(NOXRED1):​c.884G>A​(p.Gly295Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,948 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

NOXRED1
NM_001113475.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.749
Variant links:
Genes affected
NOXRED1 (HGNC:20487): (NADP dependent oxidoreductase domain containing 1) Predicted to enable pyrroline-5-carboxylate reductase activity. Predicted to be involved in L-proline biosynthetic process. [provided by Alliance of Genome Resources, Apr 2022]

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=0.076292604).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NOXRED1NM_001113475.3 linkc.884G>A p.Gly295Asp missense_variant Exon 5 of 6 ENST00000380835.7 NP_001106946.1 Q6NXP6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NOXRED1ENST00000380835.7 linkc.884G>A p.Gly295Asp missense_variant Exon 5 of 6 1 NM_001113475.3 ENSP00000370215.2 Q6NXP6-1
NOXRED1ENST00000555901.1 linkn.1639G>A non_coding_transcript_exon_variant Exon 4 of 5 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000121
AC:
3
AN:
248690
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135142
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000266
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1459948
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
726358
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:
0.00000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000468
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 26, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.884G>A (p.G295D) alteration is located in exon 5 (coding exon 5) of the NOXRED1 gene. This alteration results from a G to A substitution at nucleotide position 884, causing the glycine (G) at amino acid position 295 to be replaced by an aspartic acid (D). 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
0.23
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
14
DANN
Uncertain
0.97
DEOGEN2
Benign
0.039
T
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.63
FATHMM_MKL
Benign
0.055
N
LIST_S2
Benign
0.48
T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.076
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.90
N
REVEL
Benign
0.056
Sift
Benign
0.13
T
Sift4G
Benign
0.29
T
Polyphen
0.17
B
Vest4
0.26
MutPred
0.53
Loss of sheet (P = 0.0054);
MVP
0.40
MPC
0.21
ClinPred
0.076
T
GERP RS
3.7
Varity_R
0.046
gMVP
0.54

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: rs1392499215; hg19: chr14-77872277; API