Variant 9-137212587-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_014434.4(NDOR1):c.299C>A(p.Ser100Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NDOR1
NM_014434.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.41

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 made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.937

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDOR1	NM_014434.4 link	c.299C>A	p.Ser100Tyr	missense_variant	Exon 3 of 14	ENST00000684003.1	NP_055249.1	Q9UHB4-1
NDOR1	NM_001144026.3 link	c.299C>A	p.Ser100Tyr	missense_variant	Exon 3 of 14		NP_001137498.1	Q9UHB4-2
NDOR1	NM_001144028.3 link	c.299C>A	p.Ser100Tyr	missense_variant	Exon 3 of 14		NP_001137500.1	Q9UHB4-4
NDOR1	NM_001144027.3 link	c.299C>A	p.Ser100Tyr	missense_variant	Exon 3 of 13		NP_001137499.1	Q9UHB4-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDOR1	ENST00000684003.1 link	c.299C>A	p.Ser100Tyr	missense_variant	Exon 3 of 14		NM_014434.4	ENSP00000507194.1		Q9UHB4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461432

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727052

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 04, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.299C>A (p.S100Y) alteration is located in exon 3 (coding exon 3) of the NDOR1 gene. This alteration results from a C to A substitution at nucleotide position 299, causing the serine (S) at amino acid position 100 to be replaced by a tyrosine (Y). 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

Pathogenic

0.79

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

.;.;.;T

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Pathogenic

0.34

MetaRNN

Pathogenic

0.94

D;D;D;D

MetaSVM

Uncertain

0.72

MutationAssessor

Pathogenic

4.3

H;H;H;H

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-5.8

D;D;D;D

REVEL

Pathogenic

0.78

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;.;.;D

Vest4

0.75

MutPred

0.80

Gain of methylation at K104 (P = 0.1252);Gain of methylation at K104 (P = 0.1252);Gain of methylation at K104 (P = 0.1252);Gain of methylation at K104 (P = 0.1252);

MVP

0.94

MPC

0.85

ClinPred

1.0

GERP RS

4.1

Varity_R

0.98

gMVP

0.87

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over