rs140233506

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 1675722.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369691.1. 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
	DHPS	NM_001930.4	MANE Select	c.1074G>A	p.Lys358Lys	synonymous	Exon 9 of 9	NP_001921.1	P49366-1
	DHPS	NM_001369691.1		c.1010G>A	p.Arg337Lys	missense	Exon 9 of 9	NP_001356620.1
	DHPS	NM_001369692.1		c.787G>A	p.Asp263Asn	missense splice_region	Exon 7 of 7	NP_001356621.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHPS	ENST00000210060.12	TSL:1 MANE Select	c.1074G>A	p.Lys358Lys	synonymous	Exon 9 of 9	ENSP00000210060.6	P49366-1
	DHPS	ENST00000351660.9	TSL:1	c.933G>A	p.Lys311Lys	synonymous	Exon 8 of 8	ENSP00000221303.5	P49366-2
	DHPS	ENST00000601537.5	TSL:1	n.*136G>A		non_coding_transcript_exon	Exon 8 of 8	ENSP00000472122.1	Q5J8M5

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

GnomAD2 exomes AF: 0.00118 AC: 292 AN: 247586 AF XY: 0.00109

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 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

African (AFR) AF: 0.000120 AC: 4 AN: 33356

American (AMR) AF: 0.000929 AC: 41 AN: 44112

Ashkenazi Jewish (ASJ) AF: 0.000116 AC: 3 AN: 25816

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.00 AC: 0 AN: 85712

European-Finnish (FIN) AF: 0.00180 AC: 96 AN: 53274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00117 AC: 1303 AN: 1109874

Other (OTH) AF: 0.000880 AC: 53 AN: 60196

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

African (AFR) AF: 0.000169 AC: 7 AN: 41540

American (AMR) AF: 0.00105 AC: 16 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00170 AC: 116 AN: 68036

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000856 Hom.: 1

Bravo AF: 0.000842

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.8
DANN	Benign	0.70
PhyloP100		0.11
PromoterAI		-0.012	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs140233506; hg19: chr19-12786688;