19-48935106-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014475.4(DHDH):c.197G>T(p.Ser66Ile) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S66N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DHDH NM_014475.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.21

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12781116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHDH	NM_014475.4	c.197G>T	p.Ser66Ile	missense_variant	2/7	ENST00000221403.7
DHDH	XM_047438617.1	c.197G>T	p.Ser66Ile	missense_variant	2/5
DHDH	XM_005258748.5	c.25G>T	p.Ala9Ser	missense_variant	2/6
DHDH	XM_017026598.2	c.-53G>T		5_prime_UTR_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHDH	ENST00000221403.7	c.197G>T	p.Ser66Ile	missense_variant	2/7	1	NM_014475.4	P1
DHDH	ENST00000522614.5	c.197G>T	p.Ser66Ile	missense_variant	2/5	5
DHDH	ENST00000523250.5	c.197G>T	p.Ser66Ile	missense_variant	2/5	5
DHDH	ENST00000520557.1	c.161G>T	p.Ser54Ile	missense_variant, NMD_transcript_variant	2/5	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1411596 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 698274

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.086	T;.;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.0	D;N;D
REVEL	Benign	0.10
Sift	Uncertain	0.0030	D;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		0.085	B;.;.
Vest4		0.21
MutPred		0.46		Loss of disorder (P = 0.0173);Loss of disorder (P = 0.0173);Loss of disorder (P = 0.0173);
MVP		0.24
MPC		0.17
ClinPred		0.92	D
GERP RS		4.7
Varity_R		0.29
gMVP		0.34

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: rs2270941; hg19: chr19-49438363;