Genetic Variant NOXRED1:p.Asn233Lys (chr14-77406119-A-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001113475.3(NOXRED1):c.699T>A(p.Asn233Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000701 in 1,611,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

NOXRED1
NM_001113475.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.163

Publications

0 publications found

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]

NOXRED1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024363428).

BP6

Variant 14-77406119-A-T is Benign according to our data. Variant chr14-77406119-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3407063.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113475.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOXRED1	NM_001113475.3	MANE Select	c.699T>A	p.Asn233Lys	missense	Exon 5 of 6	NP_001106946.1	Q6NXP6-1
	NOXRED1	NM_001394980.1		c.699T>A	p.Asn233Lys	missense	Exon 6 of 7	NP_001381909.1	Q6NXP6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOXRED1	ENST00000380835.7	TSL:1 MANE Select	c.699T>A	p.Asn233Lys	missense	Exon 5 of 6	ENSP00000370215.2	Q6NXP6-1
	NOXRED1	ENST00000555901.1	TSL:2	n.1454T>A		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes

AF:

0.000453

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000178

AC:

AN:

247806

AF XY:

0.000163

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00125

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000302

AC:

AN:

1459244

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

726042

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33438

American (AMR)

AF:

0.000874

AC:

AN:

44608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86092

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1109878

Other (OTH)

AF:

0.0000166

AC:

AN:

60292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000453

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000632

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.00445

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68044

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000348

ExAC

AF:

0.0000249

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.087

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.50

M_CAP

Benign

0.028

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PhyloP100

-0.16

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.15

Sift

Benign

0.16

Sift4G

Benign

0.13

Polyphen

0.73

Vest4

0.28

MutPred

0.63

Gain of catalytic residue at N233 (P = 0)

MVP

0.12

MPC

0.55

ClinPred

0.17

GERP RS

-1.3

Varity_R

0.091

gMVP

0.73

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over