DHPS p.Ser204Ser

Variant names:

• chr19-12679522-T-T
• NM_001930.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr19-12679523--
• chr19-12679523-A-G
• chr19-12679523-A-T
• chr19-12679523-A-C
• chr19-12679524-GA-CT
• chr19-12679523-AGA-GCT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001930.4(DHPS):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DHPS NM_001930.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.486
• Publications: 0 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]

DHPS Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with seizures and speech and walking impairment

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina

ENSG00000285589 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001930.4. 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
	DHPS	NM_001930.4	MANE Select	c.		exon_region	Exon 5 of 9	NP_001921.1	P49366-1
	DHPS	NM_001369691.1		c.		exon_region	Exon 5 of 9	NP_001356620.1
	DHPS	NM_001206974.2		c.		exon_region	Exon 5 of 9	NP_001193903.1	P49366-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHPS	ENST00000210060.12	TSL:1 MANE Select	c.		exon_region	Exon 5 of 9	ENSP00000210060.6	P49366-1
	DHPS	ENST00000351660.9	TSL:1	c.		exon_region	Exon 5 of 8	ENSP00000221303.5	P49366-2
	DHPS	ENST00000601537.5	TSL:1	n.		exon_region	Exon 5 of 8	ENSP00000472122.1	Q5J8M5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49

Splicing

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

hg19: chr19-12790336;