19-48935022-A-G

Variant names:

• chr19-48935022-A-G
• rs200821290
• NM_014475.4:c.113A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014475.4(DHDH):​c.113A>G​(p.Asp38Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DHDH NM_014475.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.33

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32074618).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHDH	NM_014475.4	c.113A>G	p.Asp38Gly	missense_variant	Exon 2 of 7	ENST00000221403.7	NP_055290.1
DHDH	XM_047438617.1	c.113A>G	p.Asp38Gly	missense_variant	Exon 2 of 5		XP_047294573.1
DHDH	XM_017026598.2	c.-137A>G		5_prime_UTR_variant	Exon 2 of 7		XP_016882087.1
DHDH	XM_005258748.5	c.-60A>G		5_prime_UTR_variant	Exon 2 of 6		XP_005258805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHDH	ENST00000221403.7	c.113A>G	p.Asp38Gly	missense_variant	Exon 2 of 7	1	NM_014475.4	ENSP00000221403.2
DHDH	ENST00000522614.5	c.113A>G	p.Asp38Gly	missense_variant	Exon 2 of 5	5		ENSP00000428672.1
DHDH	ENST00000523250.5	c.113A>G	p.Asp38Gly	missense_variant	Exon 2 of 5	5		ENSP00000428935.1
DHDH	ENST00000520557.1	n.77A>G		non_coding_transcript_exon_variant	Exon 2 of 5	5		ENSP00000430360.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.066	T;.;.
Eigen	Benign	0.019
Eigen_PC	Benign	0.10
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Benign	0.19
Sift	Benign	0.031	D;T;T
Sift4G	Benign	0.13	T;T;T
Polyphen		0.028	B;.;.
Vest4		0.34
MutPred		0.59		Gain of MoRF binding (P = 0.0235);Gain of MoRF binding (P = 0.0235);Gain of MoRF binding (P = 0.0235);
MVP		0.30
MPC		0.51
ClinPred		0.91	D
GERP RS		5.0
Varity_R		0.36
gMVP		0.51

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

Other links and lift over

dbSNP: rs200821290; hg19: chr19-49438279;