9-137206251-C-A

Variant names:

• chr9-137206251-C-A
• rs760447962
• NM_014434.4:c.155C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NDOR1 NM_014434.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.95

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25898796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDOR1	NM_014434.4	c.155C>A	p.Pro52His	missense_variant	Exon 2 of 14	ENST00000684003.1	NP_055249.1
NDOR1	NM_001144026.3	c.155C>A	p.Pro52His	missense_variant	Exon 2 of 14		NP_001137498.1
NDOR1	NM_001144028.3	c.155C>A	p.Pro52His	missense_variant	Exon 2 of 14		NP_001137500.1
NDOR1	NM_001144027.3	c.155C>A	p.Pro52His	missense_variant	Exon 2 of 13		NP_001137499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDOR1	ENST00000684003.1	c.155C>A	p.Pro52His	missense_variant	Exon 2 of 14		NM_014434.4	ENSP00000507194.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251468 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135914

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 SAS exome AF: 0.00

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: 1 AN: 1461696 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727122

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.026	.;.;.;T
Eigen	Benign	-0.080
Eigen_PC	Benign	0.071
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T;T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.3	L;L;L;L
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.1	D;D;D;D
REVEL	Benign	0.089
Sift	Benign	0.088	T;T;T;T
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.0040	B;.;.;B
Vest4		0.45
MutPred		0.53		Loss of stability (P = 0.0672);Loss of stability (P = 0.0672);Loss of stability (P = 0.0672);Loss of stability (P = 0.0672);
MVP		0.63
MPC		0.24
ClinPred		0.79	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.39
gMVP		0.42

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

LitVar

Other links and lift over

dbSNP: rs760447962; hg19: chr9-140100703;