19-48944456-G-C

Variant names:

• chr19-48944456-G-C
• rs3765148
• NM_014475.4:c.844G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014475.4(DHDH):​c.844G>C​(p.Gly282Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DHDH NM_014475.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 0 publications found

Genes affected

DHDH (HGNC:17887): (dihydrodiol dehydrogenase) This gene encodes an enzyme that belongs to the family of dihydrodiol dehydrogenases, which exist in multiple forms in mammalian tissues and are involved in the metabolism of xenobiotics and sugars. These enzymes catalyze the NADP1-linked oxidation of transdihydrodiols of aromatic hydrocarbons to corresponding catechols. This enzyme is a dimeric dihydrodiol dehydrogenase, and it differs from monomeric dihydrodiol dehydrogenases in its high substrate specificity for trans-dihydrodiols of aromatic hydrocarbons in the oxidative direction. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1293537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHDH	NM_014475.4	c.844G>C	p.Gly282Arg	missense_variant	Exon 6 of 7	ENST00000221403.7	NP_055290.1
DHDH	XM_017026598.2	c.595G>C	p.Gly199Arg	missense_variant	Exon 6 of 7		XP_016882087.1
DHDH	XM_005258748.5	c.508G>C	p.Gly170Arg	missense_variant	Exon 5 of 6		XP_005258805.1
DHDH	XM_047438617.1	c.*47G>C		3_prime_UTR_variant	Exon 5 of 5		XP_047294573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHDH	ENST00000221403.7	c.844G>C	p.Gly282Arg	missense_variant	Exon 6 of 7	1	NM_014475.4	ENSP00000221403.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Uncertain	0.97
DEOGEN2	Benign	0.040	T;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.
PhyloP100		1.1
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.083
Sift	Uncertain	0.026	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		1.0	D;.
Vest4		0.21
MutPred		0.23		Gain of solvent accessibility (P = 0.0789);.;
MVP		0.39
MPC		0.62
ClinPred		0.82	D
GERP RS		0.086
Varity_R		0.082
gMVP		0.79
Mutation Taster		=99/1	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: rs3765148; hg19: chr19-49447713;