19-12677283-C-A

Variant names:

• chr19-12677283-C-A
• rs189109985
• NM_001930.4:c.784+8G>T

Variant summary

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

The NM_001930.4(DHPS):​c.784+8G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00737 in 1,613,910 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0076 (51 hom.)
• Consequence: DHPS NM_001930.4 splice_region, intron
• Scores: Splicing: ADA: 0.0005020
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.74

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:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 19-12677283-C-A is Benign according to our data. Variant chr19-12677283-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2571030.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHPS	NM_001930.4	c.784+8G>T		splice_region_variant, intron_variant	Intron 6 of 8	ENST00000210060.12	NP_001921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHPS	ENST00000210060.12	c.784+8G>T		splice_region_variant, intron_variant	Intron 6 of 8	1	NM_001930.4	ENSP00000210060.6
ENSG00000285589	ENST00000648033.1	n.*329+8G>T		splice_region_variant, intron_variant	Intron 6 of 13			ENSP00000498000.1

Frequencies

GnomAD3 genomes AF: 0.00482 AC: 734 AN: 152136 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00753

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00788

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00516 AC: 1297 AN: 251394 Hom.: 9 AF XY: 0.00526 AC XY: 715 AN XY: 135876

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000947

Gnomad FIN exome AF: 0.00726

Gnomad NFE exome AF: 0.00854

Gnomad OTH exome AF: 0.00636

GnomAD4 exome AF: 0.00764 AC: 11160 AN: 1461658 Hom.: 51 Cov.: 31 AF XY: 0.00738 AC XY: 5366 AN XY: 727140

Gnomad4 AFR exome AF: 0.00131

Gnomad4 AMR exome AF: 0.00221

Gnomad4 ASJ exome AF: 0.00199

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000916

Gnomad4 FIN exome AF: 0.00695

Gnomad4 NFE exome AF: 0.00913

Gnomad4 OTH exome AF: 0.00598

GnomAD4 genome AF: 0.00482 AC: 734 AN: 152252 Hom.: 2 Cov.: 32 AF XY: 0.00476 AC XY: 354 AN XY: 74430

Gnomad4 AFR AF: 0.00104

Gnomad4 AMR AF: 0.00393

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00753

Gnomad4 NFE AF: 0.00788

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00267 Hom.: 0

Bravo AF: 0.00442

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00791

EpiControl AF: 0.00670

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

DHPS-related disorder Benign:1

Nov 06, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DHPS: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.4
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00050
dbscSNV1_RF	Benign	0.032
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

Publications

LitVar

Other links and lift over

dbSNP: rs189109985; hg19: chr19-12788097;