Genetic Variant NM_014434.4:c.155C>A (chr9-137206251-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014434.4(NDOR1):c.155C>A(p.Pro52His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,696 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. 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. P52L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NDOR1
NM_014434.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.95

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25898796).

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.155C>A	p.Pro52His	missense	Exon 2 of 14	NP_055249.1	Q9UHB4-1
NDOR1	NM_001144026.3		c.155C>A	p.Pro52His	missense	Exon 2 of 14	NP_001137498.1	Q9UHB4-2
NDOR1	NM_001144028.3		c.155C>A	p.Pro52His	missense	Exon 2 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.155C>A	p.Pro52His	missense	Exon 2 of 14	ENSP00000507194.1	Q9UHB4-1
NDOR1	ENST00000371521.8	TSL:1	c.155C>A	p.Pro52His	missense	Exon 2 of 14	ENSP00000360576.4	Q9UHB4-2
NDOR1	ENST00000458322.2	TSL:1	c.155C>A	p.Pro52His	missense	Exon 2 of 14	ENSP00000389905.1	Q9UHB4-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251468

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461696

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727122

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111964

Other (OTH)

AF:

0.00

AC:

AN:

60386

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.026

Eigen

Benign

-0.080

Eigen_PC

Benign

0.071

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.82

M_CAP

Benign

0.026

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.3

PhyloP100

2.9

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.089

Sift

Benign

0.088

Sift4G

Benign

0.15

Polyphen

0.0040

Vest4

0.45

MutPred

0.53

Loss of stability (P = 0.0672)

MVP

0.63

MPC

0.24

ClinPred

0.79

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.39

gMVP

0.42

Mutation Taster

=61/39

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over