rs35129924

Variant names:

• chr19-12679523-A-G
• rs35129924
• NM_001930.4:c.612T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-12679523-A-G
• chr19-12679523-A-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_001930.4(DHPS):​c.612T>C​(p.Ser204Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000768 in 1,614,214 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0040 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00043 (3 hom.)
• Consequence: DHPS NM_001930.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.486
• 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]

DHPS Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with seizures and speech and walking impairment

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

ENSG00000285589 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 19-12679523-A-G is Benign according to our data. Variant chr19-12679523-A-G is described in ClinVar as Benign. ClinVar VariationId is 3035505.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.486 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000428 (626/1461890) while in subpopulation AFR AF = 0.0161 (540/33480). AF 95% confidence interval is 0.015. There are 3 homozygotes in GnomAdExome4. There are 272 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

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>C	p.Ser204Ser	synonymous	Exon 5 of 9	NP_001921.1	P49366-1
	DHPS	NM_001369691.1		c.612T>C	p.Ser204Ser	synonymous	Exon 5 of 9	NP_001356620.1
	DHPS	NM_001206974.2		c.486T>C	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>C	p.Ser204Ser	synonymous	Exon 5 of 9	ENSP00000210060.6	P49366-1
	DHPS	ENST00000351660.9	TSL:1	c.612T>C	p.Ser204Ser	synonymous	Exon 5 of 8	ENSP00000221303.5	P49366-2
	DHPS	ENST00000601537.5	TSL:1	n.612T>C		non_coding_transcript_exon	Exon 5 of 8	ENSP00000472122.1	Q5J8M5

Frequencies

GnomAD3 genomes AF: 0.00403 AC: 613 AN: 152206 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00111 AC: 279 AN: 251492 AF XY: 0.000868

Gnomad AFR exome AF: 0.0156

Gnomad AMR exome AF: 0.000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000439

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000428 AC: 626 AN: 1461890 Hom.: 3 Cov.: 32 AF XY: 0.000374 AC XY: 272 AN XY: 727246

African (AFR) AF: 0.0161 AC: 540 AN: 33480

American (AMR) AF: 0.000581 AC: 26 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000719 AC: 8 AN: 1112008

Other (OTH) AF: 0.000811 AC: 49 AN: 60396

GnomAD4 genome AF: 0.00403 AC: 614 AN: 152324 Hom.: 7 Cov.: 32 AF XY: 0.00383 AC XY: 285 AN XY: 74466

African (AFR) AF: 0.0141 AC: 587 AN: 41574

American (AMR) AF: 0.000915 AC: 14 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68026

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00167 Hom.: 4

Bravo AF: 0.00441

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DHPS-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.0
DANN	Benign	0.57
PhyloP100		0.49
PromoterAI		0.030	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs35129924; hg19: chr19-12790337;