chr9-137205850-G-C

Variant names:

• chr9-137205850-G-C
• rs367940263
• NM_014434.4:c.73G>C

Variant summary

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

The NM_014434.4(NDOR1):​c.73G>C​(p.Gly25Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,450,840 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NDOR1 NM_014434.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.88

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]

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

ACMG classification

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	c.73G>C	p.Gly25Arg	missense_variant	Exon 1 of 14	ENST00000684003.1	NP_055249.1
TMEM203	NM_053045.2	c.-436C>G		upstream_gene_variant		ENST00000343666.6	NP_444273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDOR1	ENST00000684003.1	c.73G>C	p.Gly25Arg	missense_variant	Exon 1 of 14		NM_014434.4	ENSP00000507194.1
TMEM203	ENST00000343666.6	c.-436C>G		upstream_gene_variant		6	NM_053045.2	ENSP00000375053.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000431 AC: 1 AN: 231772 Hom.: 0 AF XY: 0.00000780 AC XY: 1 AN XY: 128260

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000956

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1450840 Hom.: 0 Cov.: 34 AF XY: 0.00000277 AC XY: 2 AN XY: 721960

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.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	.;.;.;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Pathogenic	0.47	D
MetaRNN	Uncertain	0.51	D;D;D;D
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	2.0	M;M;M;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.1	D;D;D;D
REVEL	Uncertain	0.38
Sift	Benign	0.10	T;T;T;T
Sift4G	Benign	0.10	T;T;T;T
Polyphen		0.75	P;.;.;B
Vest4		0.47
MutPred		0.57		Gain of MoRF binding (P = 0.0255);Gain of MoRF binding (P = 0.0255);Gain of MoRF binding (P = 0.0255);Gain of MoRF binding (P = 0.0255);
MVP		0.87
MPC		0.45
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.94
gMVP		0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs367940263; hg19: chr9-140100302;