19-48939676-T-C

Variant names:

• chr19-48939676-T-C
• rs2270939
• NM_014475.4:c.594T>C
• DHDH p.Ser198Ser

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014475.4(DHDH):​c.594T>C​(p.Ser198Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,603,172 control chromosomes in the GnomAD database, including 53,048 homozygotes. 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: 𝑓 0.34 (11900 hom., cov: 31)
  • Exomes 𝑓: 0.21 (41148 hom.)
• Consequence: DHDH NM_014475.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP7: Synonymous conserved (PhyloP=-2.63 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014475.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHDH	NM_014475.4	MANE Select	c.594T>C	p.Ser198Ser	synonymous	Exon 4 of 7	NP_055290.1	Q9UQ10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHDH	ENST00000221403.7	TSL:1 MANE Select	c.594T>C	p.Ser198Ser	synonymous	Exon 4 of 7	ENSP00000221403.2	Q9UQ10
	DHDH	ENST00000522614.5	TSL:5	c.594T>C	p.Ser198Ser	synonymous	Exon 4 of 5	ENSP00000428672.1	E5RGT8
	DHDH	ENST00000523250.5	TSL:5	c.203-2764T>C		intron	N/A	ENSP00000428935.1	E5RFE0

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51593 AN: 151890 Hom.: 11852 Cov.: 31

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.301

GnomAD2 exomes AF: 0.281 AC: 70016 AN: 249440 AF XY: 0.272

Gnomad AFR exome AF: 0.646

Gnomad AMR exome AF: 0.273

Gnomad ASJ exome AF: 0.187

Gnomad EAS exome AF: 0.556

Gnomad FIN exome AF: 0.314

Gnomad NFE exome AF: 0.172

Gnomad OTH exome AF: 0.235

GnomAD4 exome AF: 0.212 AC: 307976 AN: 1451164 Hom.: 41148 Cov.: 32 AF XY: 0.214 AC XY: 153967 AN XY: 719718

African (AFR) AF: 0.653 AC: 21679 AN: 33224

American (AMR) AF: 0.274 AC: 12061 AN: 44070

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 4834 AN: 25928

East Asian (EAS) AF: 0.551 AC: 21707 AN: 39424

South Asian (SAS) AF: 0.348 AC: 29932 AN: 86046

European-Finnish (FIN) AF: 0.306 AC: 16234 AN: 53108

Middle Eastern (MID) AF: 0.205 AC: 1177 AN: 5728

European-Non Finnish (NFE) AF: 0.168 AC: 185592 AN: 1103796

Other (OTH) AF: 0.247 AC: 14760 AN: 59840

GnomAD4 genome AF: 0.340 AC: 51704 AN: 152008 Hom.: 11900 Cov.: 31 AF XY: 0.346 AC XY: 25728 AN XY: 74302

African (AFR) AF: 0.637 AC: 26368 AN: 41426

American (AMR) AF: 0.265 AC: 4053 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 677 AN: 3470

East Asian (EAS) AF: 0.561 AC: 2894 AN: 5160

South Asian (SAS) AF: 0.371 AC: 1791 AN: 4824

European-Finnish (FIN) AF: 0.328 AC: 3462 AN: 10558

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11620 AN: 67990

Other (OTH) AF: 0.305 AC: 642 AN: 2104

Alfa AF: 0.212 Hom.: 7721

Bravo AF: 0.348

Asia WGS AF: 0.478 AC: 1660 AN: 3478

EpiCase AF: 0.171

EpiControl AF: 0.164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.045
DANN	Benign	0.25
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2270939;

hg19: chr19-49442933;

COSMIC: COSV55481591;