chr19-48939676-T-A

Variant names:

• chr19-48939676-T-A
• rs2270939
• NM_014475.4:c.594T>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014475.4(DHDH):​c.594T>A​(p.Ser198Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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: 31)
• Consequence: DHDH NM_014475.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-2.63 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHDH	NM_014475.4	c.594T>A	p.Ser198Ser	synonymous_variant	Exon 4 of 7	ENST00000221403.7	NP_055290.1
DHDH	XM_017026598.2	c.345T>A	p.Ser115Ser	synonymous_variant	Exon 4 of 7		XP_016882087.1
DHDH	XM_047438617.1	c.594T>A	p.Ser198Ser	synonymous_variant	Exon 4 of 5		XP_047294573.1
DHDH	XM_005258748.5	c.258T>A	p.Ser86Ser	synonymous_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.594T>A	p.Ser198Ser	synonymous_variant	Exon 4 of 7	1	NM_014475.4	ENSP00000221403.2
DHDH	ENST00000522614.5	c.594T>A	p.Ser198Ser	synonymous_variant	Exon 4 of 5	5		ENSP00000428672.1
DHDH	ENST00000520557.1	n.394T>A		non_coding_transcript_exon_variant	Exon 3 of 5	5		ENSP00000430360.1
DHDH	ENST00000523250.5	c.203-2764T>A		intron_variant	Intron 2 of 4	5		ENSP00000428935.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.038
DANN	Benign	0.39
PhyloP100		-2.6

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

Other links and lift over

dbSNP: rs2270939; hg19: chr19-49442933;