19-48939581-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_014475.4(DHDH):c.499C>T(p.Arg167Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000305 in 1,608,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000048 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

DHDH
NM_014475.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.42

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06990191).

BP6

Variant 19-48939581-C-T is Benign according to our data. Variant chr19-48939581-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2371912.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHDH	NM_014475.4 link	c.499C>T	p.Arg167Trp	missense_variant	Exon 4 of 7	ENST00000221403.7	NP_055290.1	Q9UQ10
DHDH	XM_017026598.2 link	c.250C>T	p.Arg84Trp	missense_variant	Exon 4 of 7		XP_016882087.1
DHDH	XM_047438617.1 link	c.499C>T	p.Arg167Trp	missense_variant	Exon 4 of 5		XP_047294573.1
DHDH	XM_005258748.5 link	c.163C>T	p.Arg55Trp	missense_variant	Exon 3 of 6		XP_005258805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DHDH	ENST00000221403.7 link	c.499C>T	p.Arg167Trp	missense_variant	Exon 4 of 7	1	NM_014475.4	ENSP00000221403.2	Q9UQ10
DHDH	ENST00000522614.5 link	c.499C>T	p.Arg167Trp	missense_variant	Exon 4 of 5	5		ENSP00000428672.1	E5RGT8
DHDH	ENST00000523250.5 link	c.203-2859C>T		intron_variant	Intron 2 of 4	5		ENSP00000428935.1	E5RFE0
DHDH	ENST00000520557.1 link	n.299C>T		non_coding_transcript_exon_variant	Exon 3 of 5	5		ENSP00000430360.1	H0YBU7

Frequencies

GnomAD3 genomes

AF:

0.0000477

AC:

AN:

146726

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000122

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:

0.0000300

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000484

AC:

AN:

248064

Hom.:

AF XY:

0.0000671

AC XY:

AN XY:

134202

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.0000875

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000663

Gnomad FIN exome

AF:

0.0000466

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000287

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000477

AC:

AN:

146726

Hom.:

Cov.:

AF XY:

0.0000703

AC XY:

AN XY:

71130

show subpopulations

Gnomad4 AFR

AF:

0.000122

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:

0.0000300

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000491

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 06, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.16

T;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.34

T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.070

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.065

N;.

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.067

Sift

Benign

0.16

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.015

B;.

Vest4

0.17

MVP

0.18

MPC

0.13

ClinPred

0.059

GERP RS

3.0

Varity_R

0.074

gMVP

0.57

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over