chr9-137213996-G-A

Variant names:

• chr9-137213996-G-A
• rs151228457
• NM_014434.4:c.440G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014434.4(NDOR1):​c.440G>A​(p.Arg147Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,554,914 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R147P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: NDOR1 NM_014434.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0043888986).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014434.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDOR1	NM_014434.4	MANE Select	c.440G>A	p.Arg147Gln	missense	Exon 5 of 14	NP_055249.1	Q9UHB4-1
	NDOR1	NM_001144026.3		c.440G>A	p.Arg147Gln	missense	Exon 5 of 14	NP_001137498.1	Q9UHB4-2
	NDOR1	NM_001144028.3		c.440G>A	p.Arg147Gln	missense	Exon 5 of 14	NP_001137500.1	Q9UHB4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDOR1	ENST00000684003.1	MANE Select	c.440G>A	p.Arg147Gln	missense	Exon 5 of 14	ENSP00000507194.1	Q9UHB4-1
	NDOR1	ENST00000371521.8	TSL:1	c.440G>A	p.Arg147Gln	missense	Exon 5 of 14	ENSP00000360576.4	Q9UHB4-2
	NDOR1	ENST00000458322.2	TSL:1	c.440G>A	p.Arg147Gln	missense	Exon 5 of 14	ENSP00000389905.1	Q9UHB4-4

Frequencies

GnomAD3 genomes AF: 0.00161 AC: 245 AN: 152212 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00552

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000492 AC: 79 AN: 160728 AF XY: 0.000409

Gnomad AFR exome AF: 0.00799

Gnomad AMR exome AF: 0.0000795

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000823

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000157 AC: 220 AN: 1402584 Hom.: 1 Cov.: 32 AF XY: 0.000118 AC XY: 82 AN XY: 692906

African (AFR) AF: 0.00602 AC: 194 AN: 32222

American (AMR) AF: 0.000166 AC: 6 AN: 36248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25190

East Asian (EAS) AF: 0.00 AC: 0 AN: 36688

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 80094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45450

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5404

European-Non Finnish (NFE) AF: 0.00000554 AC: 6 AN: 1083050

Other (OTH) AF: 0.000223 AC: 13 AN: 58238

GnomAD4 genome AF: 0.00161 AC: 245 AN: 152330 Hom.: 1 Cov.: 33 AF XY: 0.00153 AC XY: 114 AN XY: 74482

African (AFR) AF: 0.00551 AC: 229 AN: 41574

American (AMR) AF: 0.000457 AC: 7 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68018

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.000809 Hom.: 1

Bravo AF: 0.00187

ESP6500AA AF: 0.00718 AC: 31

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000413 AC: 47

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.060
DANN	Benign	0.90
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.37	N
PhyloP100		-2.3
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.012
Sift	Benign	0.56	T
Sift4G	Benign	0.55	T
Polyphen		0.0010	B
Vest4		0.10
MVP		0.27
MPC		0.21
ClinPred		0.0023	T
GERP RS		-2.8
Varity_R		0.051
gMVP		0.13
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs151228457; hg19: chr9-140108448;