Variant 19-48939467-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_014475.4(DHDH):c.385T>G(p.Phe129Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

DHDH
NM_014475.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.21

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.762

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DHDH	NM_014475.4 linkuse as main transcript	c.385T>G	p.Phe129Val	missense_variant	4/7	ENST00000221403.7
DHDH	XM_017026598.2 linkuse as main transcript	c.136T>G	p.Phe46Val	missense_variant	4/7
DHDH	XM_047438617.1 linkuse as main transcript	c.385T>G	p.Phe129Val	missense_variant	4/5
DHDH	XM_005258748.5 linkuse as main transcript	c.49T>G	p.Phe17Val	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DHDH	ENST00000221403.7 linkuse as main transcript	c.385T>G	p.Phe129Val	missense_variant	4/7	1	NM_014475.4	P1
DHDH	ENST00000522614.5 linkuse as main transcript	c.385T>G	p.Phe129Val	missense_variant	4/5	5
DHDH	ENST00000523250.5 linkuse as main transcript	c.203-2973T>G		intron_variant		5
DHDH	ENST00000520557.1 linkuse as main transcript	c.185T>G	p.Leu62Arg	missense_variant, NMD_transcript_variant	3/5	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2023

The c.385T>G (p.F129V) alteration is located in exon 4 (coding exon 4) of the DHDH gene. This alteration results from a T to G substitution at nucleotide position 385, causing the phenylalanine (F) at amino acid position 129 to be replaced by a valine (V). 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

Pathogenic

0.64

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;.

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.012

MetaRNN

Pathogenic

0.76

D;D

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.7

M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-6.8

D;D

REVEL

Uncertain

0.45

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.85

MutPred

0.55

Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);

MVP

0.33

MPC

0.57

ClinPred

1.0

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.90

gMVP

0.71

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over