chr19-48939593-G-A

Variant names:

• chr19-48939593-G-A
• NM_014475.4:c.511G>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_014475.4(DHDH):​c.511G>A​(p.Gly171Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DHDH NM_014475.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.93

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

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.971

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHDH	NM_014475.4	c.511G>A	p.Gly171Arg	missense_variant	Exon 4 of 7	ENST00000221403.7	NP_055290.1
DHDH	XM_017026598.2	c.262G>A	p.Gly88Arg	missense_variant	Exon 4 of 7		XP_016882087.1
DHDH	XM_047438617.1	c.511G>A	p.Gly171Arg	missense_variant	Exon 4 of 5		XP_047294573.1
DHDH	XM_005258748.5	c.175G>A	p.Gly59Arg	missense_variant	Exon 3 of 6		XP_005258805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHDH	ENST00000221403.7	c.511G>A	p.Gly171Arg	missense_variant	Exon 4 of 7	1	NM_014475.4	ENSP00000221403.2
DHDH	ENST00000522614.5	c.511G>A	p.Gly171Arg	missense_variant	Exon 4 of 5	5		ENSP00000428672.1
DHDH	ENST00000523250.5	c.203-2847G>A		intron_variant	Intron 2 of 4	5		ENSP00000428935.1
DHDH	ENST00000520557.1	n.311G>A		non_coding_transcript_exon_variant	Exon 3 of 5	5		ENSP00000430360.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458844 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725784

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: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T;.
Eigen	Pathogenic	0.81
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Pathogenic	4.1	H;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-7.4	D;D
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;.
Vest4		0.95
MutPred		0.81		Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);
MVP		0.49
MPC		0.65
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.59
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-49442850;