19-12675874-C-T

Variant names:

• chr19-12675874-C-T
• rs140233506
• NM_001930.4:c.1074G>A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001369691.1(DHPS):​c.1010G>A​(p.Arg337Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,610,004 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (3 hom.)
• Consequence: DHPS NM_001369691.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.110

Genes affected

DHPS (HGNC:2869): (deoxyhypusine synthase) This gene encodes a protein that is required for the formation of hypusine, a unique amino acid formed by the posttranslational modification of only one protein, eukaryotic translation initiation factor 5A. The encoded protein catalyzes the first step in hypusine formation by transferring the butylamine moiety of spermidine to a specific lysine residue of the eukaryotic translation initiation factor 5A precursor, forming an intermediate deoxyhypusine residue. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2011]

ENSG00000285589 (HGNC:):

WDR83 (HGNC:32672): (WD repeat domain 83) This gene encodes a member of the WD-40 protein family. The protein is proposed to function as a molecular scaffold for various multimeric protein complexes. The protein associates with several components of the extracellular signal-regulated kinase (ERK) pathway, and promotes ERK activity in response to serum or other signals. The protein also interacts with egl nine homolog 3 (EGLN3, also known as PHD3) and regulates expression of hypoxia-inducible factor 1, and has been purified as part of the spliceosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 19-12675874-C-T is Benign according to our data. Variant chr19-12675874-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1675722.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHPS	NM_001930.4	c.1074G>A	p.Lys358Lys	synonymous_variant	Exon 9 of 9	ENST00000210060.12	NP_001921.1
WDR83	NM_001099737.3	c.*202C>T		downstream_gene_variant		ENST00000418543.8	NP_001093207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHPS	ENST00000210060.12	c.1074G>A	p.Lys358Lys	synonymous_variant	Exon 9 of 9	1	NM_001930.4	ENSP00000210060.6
ENSG00000285589	ENST00000648033.1	n.*619G>A		non_coding_transcript_exon_variant	Exon 9 of 14			ENSP00000498000.1
ENSG00000285589	ENST00000648033.1	n.*619G>A		3_prime_UTR_variant	Exon 9 of 14			ENSP00000498000.1
WDR83	ENST00000418543.8	c.*202C>T		downstream_gene_variant		1	NM_001099737.3	ENSP00000402653.3

Frequencies

GnomAD3 genomes AF: 0.00103 AC: 156 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00170

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00118 AC: 292 AN: 247586 Hom.: 0 AF XY: 0.00109 AC XY: 146 AN XY: 133766

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.00100

Gnomad ASJ exome AF: 0.000103

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00191

Gnomad NFE exome AF: 0.00184

Gnomad OTH exome AF: 0.00133

GnomAD4 exome AF: 0.00103 AC: 1500 AN: 1457724 Hom.: 3 Cov.: 32 AF XY: 0.00105 AC XY: 758 AN XY: 724934

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.000929

Gnomad4 ASJ exome AF: 0.000116

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00180

Gnomad4 NFE exome AF: 0.00117

Gnomad4 OTH exome AF: 0.000880

GnomAD4 genome AF: 0.00102 AC: 156 AN: 152280 Hom.: 0 Cov.: 32 AF XY: 0.000846 AC XY: 63 AN XY: 74468

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.00170

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00102 Hom.: 1

Bravo AF: 0.000842

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DHPS: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.8
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs140233506; hg19: chr19-12786688;