rs62587579

Variant names:

• chr9-137216103-G-A
• rs62587579
• NM_014434.4:c.1564G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014434.4(NDOR1):​c.1564G>A​(p.Val522Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0468 in 1,613,558 control chromosomes in the GnomAD database, including 2,053 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.033 (112 hom., cov: 33)
  • Exomes 𝑓: 0.048 (1941 hom.)
• Consequence: NDOR1 NM_014434.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006190866).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDOR1	NM_014434.4	c.1564G>A	p.Val522Ile	missense_variant	Exon 13 of 14	ENST00000684003.1	NP_055249.1
NDOR1	NM_001144026.3	c.1591G>A	p.Val531Ile	missense_variant	Exon 13 of 14		NP_001137498.1
NDOR1	NM_001144028.3	c.1543G>A	p.Val515Ile	missense_variant	Exon 13 of 14		NP_001137500.1
NDOR1	NM_001144027.3	c.1462G>A	p.Val488Ile	missense_variant	Exon 12 of 13		NP_001137499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDOR1	ENST00000684003.1	c.1564G>A	p.Val522Ile	missense_variant	Exon 13 of 14		NM_014434.4	ENSP00000507194.1
NDOR1	ENST00000371521.8	c.1591G>A	p.Val531Ile	missense_variant	Exon 13 of 14	1		ENSP00000360576.4
NDOR1	ENST00000458322.2	c.1543G>A	p.Val515Ile	missense_variant	Exon 13 of 14	1		ENSP00000389905.1
NDOR1	ENST00000427047.6	c.1462G>A	p.Val488Ile	missense_variant	Exon 12 of 13	2		ENSP00000394309.1

Frequencies

GnomAD3 genomes AF: 0.0333 AC: 5062 AN: 152200 Hom.: 112 Cov.: 33

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0371

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0232

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0493

Gnomad OTH AF: 0.0421

GnomAD2 exomes AF: 0.0346 AC: 8685 AN: 250934 AF XY: 0.0354

Gnomad AFR exome AF: 0.00888

Gnomad AMR exome AF: 0.0220

Gnomad ASJ exome AF: 0.0736

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.0206

Gnomad NFE exome AF: 0.0492

Gnomad OTH exome AF: 0.0372

GnomAD4 exome AF: 0.0482 AC: 70457 AN: 1461240 Hom.: 1941 Cov.: 34 AF XY: 0.0476 AC XY: 34566 AN XY: 726936

Gnomad4 AFR exome AF: 0.00959 AC: 321 AN: 33480

Gnomad4 AMR exome AF: 0.0227 AC: 1014 AN: 44720

Gnomad4 ASJ exome AF: 0.0778 AC: 2034 AN: 26136

Gnomad4 EAS exome AF: 0.000151 AC: 6 AN: 39700

Gnomad4 SAS exome AF: 0.0258 AC: 2223 AN: 86256

Gnomad4 FIN exome AF: 0.0226 AC: 1195 AN: 52796

Gnomad4 NFE exome AF: 0.0542 AC: 60274 AN: 1112000

Gnomad4 Remaining exome AF: 0.0498 AC: 3008 AN: 60384

GnomAD4 genome AF: 0.0332 AC: 5062 AN: 152318 Hom.: 112 Cov.: 33 AF XY: 0.0323 AC XY: 2407 AN XY: 74496

Gnomad4 AFR AF: 0.0107 AC: 0.0106792 AN: 0.0106792

Gnomad4 AMR AF: 0.0370 AC: 0.0369741 AN: 0.0369741

Gnomad4 ASJ AF: 0.0648 AC: 0.0648415 AN: 0.0648415

Gnomad4 EAS AF: 0.000193 AC: 0.000192901 AN: 0.000192901

Gnomad4 SAS AF: 0.0236 AC: 0.0236123 AN: 0.0236123

Gnomad4 FIN AF: 0.0232 AC: 0.0231595 AN: 0.0231595

Gnomad4 NFE AF: 0.0493 AC: 0.0492869 AN: 0.0492869

Gnomad4 OTH AF: 0.0412 AC: 0.0411542 AN: 0.0411542

Alfa AF: 0.0445 Hom.: 282

Bravo AF: 0.0326

TwinsUK AF: 0.0561 AC: 208

ALSPAC AF: 0.0553 AC: 213

ESP6500AA AF: 0.0102 AC: 45

ESP6500EA AF: 0.0544 AC: 468

ExAC AF: 0.0350 AC: 4253

Asia WGS AF: 0.0120 AC: 43 AN: 3478

EpiCase AF: 0.0525

EpiControl AF: 0.0497

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.84
DEOGEN2	Benign	0.059	.;.;.;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.55
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.85	T;D;D;D
MetaRNN	Benign	0.0062	T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.35	.;.;.;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.030	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	0.86	T;T;T;T
Polyphen		0.021	B;.;.;B
Vest4		0.067
MPC		0.17
ClinPred		0.0045	T
GERP RS		2.0
Varity_R		0.019
gMVP		0.28
Mutation Taster		=97/3	polymorphism (auto)

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

LitVar

Other links and lift over

dbSNP: rs62587579; hg19: chr9-140110555; COSMIC: COSV107438217; COSMIC: COSV107438217;