chr16-72012180-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P51L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DHODH NM_001361.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.21
• Publications: 2 publications found

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]

DHODH Gene-Disease associations (from GenCC):

• postaxial acrofacial dysostosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000294600 (HGNC:):

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_001361.5. 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
	DHODH	NM_001361.5	MANE Select	c.152C>G	p.Pro51Arg	missense	Exon 2 of 9	NP_001352.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHODH	ENST00000219240.9	TSL:1 MANE Select	c.152C>G	p.Pro51Arg	missense	Exon 2 of 9	ENSP00000219240.4	Q02127
	DHODH	ENST00000894311.1		c.152C>G	p.Pro51Arg	missense	Exon 2 of 11	ENSP00000564370.1
	DHODH	ENST00000894313.1		c.149C>G	p.Pro50Arg	missense	Exon 2 of 9	ENSP00000564372.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.48	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Pathogenic	0.97	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.2
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.46		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

Other links and lift over

dbSNP: rs372155275; hg19: chr16-72046079;