9-137212535-C-T

Variant names:

• chr9-137212535-C-T
• NM_014434.4:c.247C>T

Variant summary

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

The NM_014434.4(NDOR1):​c.247C>T​(p.Pro83Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NDOR1 NM_014434.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.46

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 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.247C>T	p.Pro83Ser	missense_variant	Exon 3 of 14	ENST00000684003.1	NP_055249.1
NDOR1	NM_001144026.3	c.247C>T	p.Pro83Ser	missense_variant	Exon 3 of 14		NP_001137498.1
NDOR1	NM_001144028.3	c.247C>T	p.Pro83Ser	missense_variant	Exon 3 of 14		NP_001137500.1
NDOR1	NM_001144027.3	c.247C>T	p.Pro83Ser	missense_variant	Exon 3 of 13		NP_001137499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDOR1	ENST00000684003.1	c.247C>T	p.Pro83Ser	missense_variant	Exon 3 of 14		NM_014434.4	ENSP00000507194.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.247C>T (p.P83S) alteration is located in exon 3 (coding exon 3) of the NDOR1 gene. This alteration results from a C to T substitution at nucleotide position 247, causing the proline (P) at amino acid position 83 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;.;.;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.83	T;D;T;T
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.5	M;M;M;M
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-7.6	D;D;D;D
REVEL	Uncertain	0.30
Sift	Benign	0.030	D;D;D;D
Sift4G	Benign	0.099	T;T;T;T
Polyphen		0.86	P;.;.;B
Vest4		0.21
MutPred		0.50		Gain of MoRF binding (P = 0.0504);Gain of MoRF binding (P = 0.0504);Gain of MoRF binding (P = 0.0504);Gain of MoRF binding (P = 0.0504);
MVP		0.87
MPC		0.38
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.83
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-140106987; COSMIC: COSV61288922; COSMIC: COSV61288922;