Genetic Variant DHDH:p.Arg107Cys (chr19-48936148-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_014475.4(DHDH):c.319C>T(p.Arg107Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,607,700 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DHDH
NM_014475.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.283

Variant links:

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]

DHDH links:

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ACMG classification

Classification made for transcript

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
DHDH	NM_014475.4 link	c.319C>T	p.Arg107Cys	missense_variant	Exon 3 of 7	ENST00000221403.7	NP_055290.1	Q9UQ10
DHDH	XM_017026598.2 link	c.70C>T	p.Arg24Cys	missense_variant	Exon 3 of 7		XP_016882087.1
DHDH	XM_047438617.1 link	c.319C>T	p.Arg107Cys	missense_variant	Exon 3 of 5		XP_047294573.1
DHDH	XM_005258748.5 link	c.30+1037C>T		intron_variant	Intron 2 of 5		XP_005258805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DHDH	ENST00000221403.7 link	c.319C>T	p.Arg107Cys	missense_variant	Exon 3 of 7	1	NM_014475.4	ENSP00000221403.2	Q9UQ10
DHDH	ENST00000522614.5 link	c.319C>T	p.Arg107Cys	missense_variant	Exon 3 of 5	5		ENSP00000428672.1	E5RGT8
DHDH	ENST00000523250.5 link	c.202+1037C>T		intron_variant	Intron 2 of 4	5		ENSP00000428935.1	E5RFE0
DHDH	ENST00000520557.1 link	n.166+1037C>T		intron_variant	Intron 2 of 4	5		ENSP00000430360.1	H0YBU7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455496

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723570

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000826

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;.

Eigen

Benign

0.14

Eigen_PC

Benign

-0.052

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.0069

MetaRNN

Uncertain

0.54

D;D

MetaSVM

Benign

-0.91

MutationAssessor

Pathogenic

3.2

M;.

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-4.8

D;D

REVEL

Benign

0.14

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

D;.

Vest4

0.48

MutPred

0.64

Loss of disorder (P = 0.0244);Loss of disorder (P = 0.0244);

MVP

0.47

MPC

0.66

ClinPred

0.97

GERP RS

4.9

Varity_R

0.40

gMVP

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over