dbSNP rs151228457: NDOR1:p.Arg147Gln (chr9-137213996-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014434.4(NDOR1):c.440G>A(p.Arg147Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,554,914 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

NDOR1
NM_014434.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.29

Variant links:

Genes affected

NDOR1 (HGNC:29838): (NADPH dependent diflavin oxidoreductase 1) This gene encodes an NADPH-dependent diflavin reductase that contains both flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) binding domains. The encoded protein catalyzes the transfer of electrons from NADPH through FAD and FMN cofactors to potential redox partners. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

NDOR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043888986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDOR1	NM_014434.4 link	c.440G>A	p.Arg147Gln	missense_variant	Exon 5 of 14	ENST00000684003.1	NP_055249.1	Q9UHB4-1
NDOR1	NM_001144026.3 link	c.440G>A	p.Arg147Gln	missense_variant	Exon 5 of 14		NP_001137498.1	Q9UHB4-2
NDOR1	NM_001144028.3 link	c.440G>A	p.Arg147Gln	missense_variant	Exon 5 of 14		NP_001137500.1	Q9UHB4-4
NDOR1	NM_001144027.3 link	c.410+118G>A		intron_variant	Intron 4 of 12		NP_001137499.1	Q9UHB4-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDOR1	ENST00000684003.1 link	c.440G>A	p.Arg147Gln	missense_variant	Exon 5 of 14		NM_014434.4	ENSP00000507194.1		Q9UHB4-1

Frequencies

GnomAD3 genomes

AF:

0.00161

AC:

245

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00552

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.0000441

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000492

AC:

AN:

160728

Hom.:

AF XY:

0.000409

AC XY:

AN XY:

85590

show subpopulations

Gnomad AFR exome

AF:

0.00799

Gnomad AMR exome

AF:

0.0000795

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000823

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000157

AC:

220

AN:

1402584

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

692906

show subpopulations

Gnomad4 AFR exome

AF:

0.00602

Gnomad4 AMR exome

AF:

0.000166

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000554

Gnomad4 OTH exome

AF:

0.000223

GnomAD4 genome

AF:

0.00161

AC:

245

AN:

152330

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

114

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00551

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000436

Hom.:

Bravo

AF:

0.00187

ESP6500AA

AF:

0.00718

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000413

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.060

DANN

Benign

0.90

DEOGEN2

Benign

0.0051

.;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.72

T;T;T

MetaRNN

Benign

0.0044

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.37

N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

0.13

N;N;N

REVEL

Benign

0.012

Sift

Benign

0.56

T;T;T

Sift4G

Benign

0.55

T;T;T

Polyphen

0.0010

B;.;B

Vest4

0.10

MVP

0.27

MPC

0.21

ClinPred

0.0023

GERP RS

-2.8

Varity_R

0.051

gMVP

0.13

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over