Variant 9-137212545-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014434.4(NDOR1):c.257C>T(p.Ala86Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000341 in 1,614,004 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 2 hom. )

Consequence

NDOR1
NM_014434.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.13

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:

NDOR1 (HGNC:):

NDOR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23564214).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDOR1	NM_014434.4 linkuse as main transcript	c.257C>T	p.Ala86Val	missense_variant	3/14	ENST00000684003.1	NP_055249.1	Q9UHB4-1
NDOR1	NM_001144026.3 linkuse as main transcript	c.257C>T	p.Ala86Val	missense_variant	3/14		NP_001137498.1	Q9UHB4-2
NDOR1	NM_001144028.3 linkuse as main transcript	c.257C>T	p.Ala86Val	missense_variant	3/14		NP_001137500.1	Q9UHB4-4
NDOR1	NM_001144027.3 linkuse as main transcript	c.257C>T	p.Ala86Val	missense_variant	3/13		NP_001137499.1	Q9UHB4-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDOR1	ENST00000684003.1 linkuse as main transcript	c.257C>T	p.Ala86Val	missense_variant	3/14		NM_014434.4	ENSP00000507194.1		Q9UHB4-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

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

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251446

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000369

AC:

AN:

1461804

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000778

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.257C>T (p.A86V) alteration is located in exon 3 (coding exon 3) of the NDOR1 gene. This alteration results from a C to T substitution at nucleotide position 257, causing the alanine (A) at amino acid position 86 to be replaced by a valine (V). 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

Benign

0.20

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.099

.;.;.;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.075

MetaRNN

Benign

0.24

T;T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.6

L;L;L;L

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.8

D;D;D;D

REVEL

Benign

0.19

Sift

Benign

0.072

T;T;T;T

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.13

B;.;.;B

Vest4

0.30

MutPred

0.59

Gain of MoRF binding (P = 0.1161);Gain of MoRF binding (P = 0.1161);Gain of MoRF binding (P = 0.1161);Gain of MoRF binding (P = 0.1161);

MVP

0.82

MPC

0.22

ClinPred

0.31

GERP RS

4.1

Varity_R

0.50

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over