Variant 9-137205831-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014434.4(NDOR1):c.54G>C(p.Gln18His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,974 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NDOR1
NM_014434.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.105

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDOR1	NM_014434.4 link	c.54G>C	p.Gln18His	missense_variant	Exon 1 of 14	ENST00000684003.1	NP_055249.1	Q9UHB4-1
TMEM203	NM_053045.2 link	c.-417C>G		upstream_gene_variant		ENST00000343666.6	NP_444273.1	Q969S6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDOR1	ENST00000684003.1 link	c.54G>C	p.Gln18His	missense_variant	Exon 1 of 14		NM_014434.4	ENSP00000507194.1		Q9UHB4-1
TMEM203	ENST00000343666.6 link	c.-417C>G		upstream_gene_variant		6	NM_053045.2	ENSP00000375053.4		Q969S6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1452974

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723174

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

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

Mar 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.54G>C (p.Q18H) alteration is located in exon 1 (coding exon 1) of the NDOR1 gene. This alteration results from a G to C substitution at nucleotide position 54, causing the glutamine (Q) at amino acid position 18 to be replaced by a histidine (H). 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

Uncertain

0.53

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

.;.;.;T

Eigen

Benign

-0.092

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.14

LIST_S2

Uncertain

0.86

D;D;D;D

M_CAP

Pathogenic

0.32

MetaRNN

Uncertain

0.46

T;T;T;T

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.9

M;M;M;M

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.8

D;D;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Benign

0.097

T;T;T;T

Polyphen

0.47

P;.;.;B

Vest4

0.37

MutPred

0.66

Loss of disorder (P = 0.0926);Loss of disorder (P = 0.0926);Loss of disorder (P = 0.0926);Loss of disorder (P = 0.0926);

MVP

0.86

MPC

0.24

ClinPred

0.99

GERP RS

1.4

Varity_R

0.72

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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