Genetic Variant NDOR1:p.Gly25Cys (chr9-137205850-G-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_014434.4(NDOR1):c.73G>T(p.Gly25Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000586 in 1,603,214 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G25S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000031 ( 1 hom. )

Consequence

NDOR1
NM_014434.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.88

Publications

2 publications found

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:

TMEM203 (HGNC:28217): (transmembrane protein 203) Involved in cellular calcium ion homeostasis. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

TMEM203 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.29922533).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014434.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDOR1	NM_014434.4	MANE Select	c.73G>T	p.Gly25Cys	missense	Exon 1 of 14	NP_055249.1	Q9UHB4-1
NDOR1	NM_001144026.3		c.73G>T	p.Gly25Cys	missense	Exon 1 of 14	NP_001137498.1	Q9UHB4-2
NDOR1	NM_001144028.3		c.73G>T	p.Gly25Cys	missense	Exon 1 of 14	NP_001137500.1	Q9UHB4-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDOR1	ENST00000684003.1	MANE Select	c.73G>T	p.Gly25Cys	missense	Exon 1 of 14	ENSP00000507194.1	Q9UHB4-1
NDOR1	ENST00000371521.8	TSL:1	c.73G>T	p.Gly25Cys	missense	Exon 1 of 14	ENSP00000360576.4	Q9UHB4-2
NDOR1	ENST00000458322.2	TSL:1	c.73G>T	p.Gly25Cys	missense	Exon 1 of 14	ENSP00000389905.1	Q9UHB4-4

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.00

GnomAD2 exomes

AF:

0.0000690

AC:

AN:

231772

AF XY:

0.0000546

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000173

GnomAD4 exome

AF:

0.0000310

AC:

AN:

1450838

Hom.:

Cov.:

AF XY:

0.0000277

AC XY:

AN XY:

721960

show subpopulations

African (AFR)

AF:

0.00129

AC:

AN:

33410

American (AMR)

AF:

0.0000224

AC:

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26084

East Asian (EAS)

AF:

0.00

AC:

AN:

39644

South Asian (SAS)

AF:

0.00

AC:

AN:

86206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5562

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110828

Other (OTH)

AF:

0.0000166

AC:

AN:

60166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000322

AC:

AN:

152376

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74524

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

41586

American (AMR)

AF:

0.000196

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.000276

ESP6500AA

AF:

0.000463

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000668

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

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

Benign

0.26

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.92

M_CAP

Pathogenic

0.65

MetaRNN

Benign

0.30

MetaSVM

Uncertain

0.013

MutationAssessor

Uncertain

2.4

PhyloP100

4.9

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-5.4

REVEL

Uncertain

0.59

Sift

Benign

0.064

Sift4G

Benign

0.098

Polyphen

1.0

Vest4

0.60

MVP

0.91

MPC

0.77

ClinPred

0.49

GERP RS

3.9

PromoterAI

0.0084

Neutral

(source)

Varity_R

0.94

gMVP

0.82

Mutation Taster

=69/31

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