rs372155275

Variant names:

• chr16-72012180-C-G
• rs372155275
• NM_001361.5:c.152C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-72012180-C-G
• chr16-72012180-C-T

Variant summary

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

The NM_001361.5(DHODH):​c.152C>G​(p.Pro51Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DHODH NM_001361.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.21

Genes affected

DHODH (HGNC:2867): (dihydroorotate dehydrogenase (quinone)) The protein encoded by this gene catalyzes the fourth enzymatic step, the ubiquinone-mediated oxidation of dihydroorotate to orotate, in de novo pyrimidine biosynthesis. This protein is a mitochondrial protein located on the outer surface of the inner mitochondrial membrane. [provided by RefSeq, Jul 2008]

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
DHODH	NM_001361.5	c.152C>G	p.Pro51Arg	missense_variant	Exon 2 of 9	ENST00000219240.9	NP_001352.2
DHODH	XM_047433674.1	c.68C>G	p.Pro23Arg	missense_variant	Exon 2 of 9		XP_047289630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHODH	ENST00000219240.9	c.152C>G	p.Pro51Arg	missense_variant	Exon 2 of 9	1	NM_001361.5	ENSP00000219240.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	24
DANN	Benign	0.91
DEOGEN2	Uncertain	0.61	.;D;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Pathogenic	0.48	D
MetaRNN	Uncertain	0.71	D;D;D
MetaSVM	Pathogenic	0.97	D
MutationAssessor	Uncertain	2.6	.;M;.
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-6.0	.;D;.
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0030	.;D;.
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.74
MutPred		0.46		Gain of MoRF binding (P = 0.057);Gain of MoRF binding (P = 0.057);.;
MVP		0.99
MPC		0.62
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.85
gMVP		0.81

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: rs372155275; hg19: chr16-72046079;