chr19-48944376-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_014475.4(DHDH):c.764G>A(p.Cys255Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
DHDH
NM_014475.4 missense
NM_014475.4 missense
Scores
4
3
12
Clinical Significance
Conservation
PhyloP100: 2.05
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]
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ACMG classification
Classification made for transcript
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=0.27349472).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DHDH | NM_014475.4 | c.764G>A | p.Cys255Tyr | missense_variant | 6/7 | ENST00000221403.7 | |
DHDH | XM_017026598.2 | c.515G>A | p.Cys172Tyr | missense_variant | 6/7 | ||
DHDH | XM_005258748.5 | c.428G>A | p.Cys143Tyr | missense_variant | 5/6 | ||
DHDH | XM_047438617.1 | c.639G>A | p.Val213= | synonymous_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DHDH | ENST00000221403.7 | c.764G>A | p.Cys255Tyr | missense_variant | 6/7 | 1 | NM_014475.4 | P1 | |
DHDH | ENST00000523250.5 | c.347G>A | p.Cys116Tyr | missense_variant | 4/5 | 5 | |||
DHDH | ENST00000522614.5 | c.620-448G>A | intron_variant | 5 | |||||
DHDH | ENST00000520557.1 | c.*25G>A | 3_prime_UTR_variant, NMD_transcript_variant | 4/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152180Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461760Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727172
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74338
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2022 | The c.764G>A (p.C255Y) alteration is located in exon 6 (coding exon 6) of the DHDH gene. This alteration results from a G to A substitution at nucleotide position 764, causing the cysteine (C) at amino acid position 255 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
P;.
Vest4
MutPred
Loss of catalytic residue at T257 (P = 0.0646);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at