19-12679523-A-T

Variant names:

• chr19-12679523-A-T
• NM_001930.4:c.612T>A
• DHPS p.Ser204Ser

Variant summary

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

The NM_001930.4(DHPS):​c.612T>A​(p.Ser204Ser) 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. Synonymous variant affecting the same amino acid position (i.e. S204S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DHPS NM_001930.4 synonymous
• 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: 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=-0.65).
• BP7: Synonymous conserved (PhyloP=0.486 with no splicing effect.

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.612T>A	p.Ser204Ser	synonymous	Exon 5 of 9	NP_001921.1	P49366-1
	DHPS	NM_001369691.1		c.612T>A	p.Ser204Ser	synonymous	Exon 5 of 9	NP_001356620.1
	DHPS	NM_001206974.2		c.486T>A	p.Ser162Ser	synonymous	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.612T>A	p.Ser204Ser	synonymous	Exon 5 of 9	ENSP00000210060.6	P49366-1
	DHPS	ENST00000351660.9	TSL:1	c.612T>A	p.Ser204Ser	synonymous	Exon 5 of 8	ENSP00000221303.5	P49366-2
	DHPS	ENST00000601537.5	TSL:1	n.612T>A		non_coding_transcript_exon	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
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.3
DANN	Benign	0.79
PhyloP100		0.49
PromoterAI		-0.0036	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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: chr19-12790337;