19-48939593-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_014475.4(DHDH):c.511G>T(p.Gly171Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,565,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000093 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

DHDH
NM_014475.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.93

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.935

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHDH	NM_014475.4 link	c.511G>T	p.Gly171Trp	missense_variant	Exon 4 of 7	ENST00000221403.7	NP_055290.1	Q9UQ10
DHDH	XM_017026598.2 link	c.262G>T	p.Gly88Trp	missense_variant	Exon 4 of 7		XP_016882087.1
DHDH	XM_047438617.1 link	c.511G>T	p.Gly171Trp	missense_variant	Exon 4 of 5		XP_047294573.1
DHDH	XM_005258748.5 link	c.175G>T	p.Gly59Trp	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.511G>T	p.Gly171Trp	missense_variant	Exon 4 of 7	1	NM_014475.4	ENSP00000221403.2	Q9UQ10
DHDH	ENST00000522614.5 link	c.511G>T	p.Gly171Trp	missense_variant	Exon 4 of 5	5		ENSP00000428672.1	E5RGT8
DHDH	ENST00000523250.5 link	c.203-2847G>T		intron_variant	Intron 2 of 4	5		ENSP00000428935.1	E5RFE0
DHDH	ENST00000520557.1 link	n.311G>T		non_coding_transcript_exon_variant	Exon 3 of 5	5		ENSP00000430360.1	H0YBU7

Frequencies

GnomAD3 genomes

AF:

0.0000935

AC:

AN:

107000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000203

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:

0.0000615

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000107

AC:

AN:

158368

Hom.:

AF XY:

0.0000820

AC XY:

AN XY:

85380

show subpopulations

Gnomad AFR exome

AF:

0.000220

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.000244

GnomAD4 exome

AF:

0.000101

AC:

147

AN:

1458844

Hom.:

Cov.:

AF XY:

0.0000882

AC XY:

AN XY:

725784

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000125

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000935

AC:

AN:

107000

Hom.:

Cov.:

AF XY:

0.0000786

AC XY:

AN XY:

50916

show subpopulations

Gnomad4 AFR

AF:

0.000203

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:

0.0000615

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000869

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.511G>T (p.G171W) alteration is located in exon 4 (coding exon 4) of the DHDH gene. This alteration results from a G to T substitution at nucleotide position 511, causing the glycine (G) at amino acid position 171 to be replaced by a tryptophan (W). 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

0.89

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Pathogenic

0.22

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

T;.

Eigen

Pathogenic

0.81

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.061

MetaRNN

Pathogenic

0.94

D;D

MetaSVM

Uncertain

-0.10

MutationAssessor

Pathogenic

4.1

H;.

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-7.4

D;D

REVEL

Pathogenic

0.66

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.93

MVP

0.51

MPC

0.64

ClinPred

0.99

GERP RS

5.1

Varity_R

0.71

gMVP

0.94

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