chr9-137213790-G-A

Variant names:

• chr9-137213790-G-A
• rs371728333
• NM_014434.4:c.322G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014434.4(NDOR1):​c.322G>A​(p.Val108Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,612,450 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: NDOR1 NM_014434.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.21
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.322G>A	p.Val108Met	missense	Exon 4 of 14	NP_055249.1	Q9UHB4-1
	NDOR1	NM_001144026.3		c.322G>A	p.Val108Met	missense	Exon 4 of 14	NP_001137498.1	Q9UHB4-2
	NDOR1	NM_001144028.3		c.322G>A	p.Val108Met	missense	Exon 4 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.322G>A	p.Val108Met	missense	Exon 4 of 14	ENSP00000507194.1	Q9UHB4-1
	NDOR1	ENST00000371521.8	TSL:1	c.322G>A	p.Val108Met	missense	Exon 4 of 14	ENSP00000360576.4	Q9UHB4-2
	NDOR1	ENST00000458322.2	TSL:1	c.322G>A	p.Val108Met	missense	Exon 4 of 14	ENSP00000389905.1	Q9UHB4-4

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000323 AC: 8 AN: 247366 AF XY: 0.0000372

Gnomad AFR exome AF: 0.000312

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1460242 Hom.: 0 Cov.: 32 AF XY: 0.0000193 AC XY: 14 AN XY: 726488

African (AFR) AF: 0.0000898 AC: 3 AN: 33414

American (AMR) AF: 0.0000674 AC: 3 AN: 44520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39666

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86196

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52766

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000990 AC: 11 AN: 1111558

Other (OTH) AF: 0.0000166 AC: 1 AN: 60302

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152208 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74346

African (AFR) AF: 0.0000724 AC: 3 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000264

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.2
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.41
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.075	T
Polyphen		1.0	D
Vest4		0.67
MVP		0.84
MPC		0.70
ClinPred		0.19	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.72
Mutation Taster		=81/19	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: rs371728333; hg19: chr9-140108242;