Variant rs35394823 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001383.6(DPH1):c.988C>G(p.Leu330Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0845 in 1,614,084 control chromosomes in the GnomAD database, including 6,333 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.068 ( 508 hom., cov: 33)

Exomes 𝑓: 0.086 ( 5825 hom. )

Consequence

DPH1
NM_001383.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.90

Variant links:

Genes affected

DPH1 (HGNC:3003): (diphthamide biosynthesis 1) The protein encoded by this gene is an enzyme involved in the biosynthesis of diphthamide, a modified histidine found only in elongation factor-2 (EEF2). Diphthamide residues in EEF2 are targeted for ADP-ribosylation by diphtheria toxin and Pseudomonas exotoxin A. Defects in this gene have been associated with both ovarian cancer and autosomal recessive intellectual disability with short stature, craniofacial, and ectodermal anomalies. [provided by RefSeq, Oct 2016]

DPH1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026078522).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPH1	NM_001383.6 link	c.988C>G	p.Leu330Val	missense_variant	9/13	ENST00000263083.12	NP_001374.4	Q9BZG8-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPH1	ENST00000263083.12 link	c.988C>G	p.Leu330Val	missense_variant	9/13	1	NM_001383.6	ENSP00000263083.7		Q9BZG8-4

Frequencies

GnomAD3 genomes

AF:

0.0683

AC:

10398

AN:

152204

Hom.:

509

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0164

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.0923

Gnomad ASJ

AF:

0.0580

Gnomad EAS

AF:

0.000960

Gnomad SAS

AF:

0.0820

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0917

Gnomad OTH

AF:

0.0607

GnomAD3 exomes

AF:

0.0811

AC:

20232

AN:

249528

Hom.:

950

AF XY:

0.0807

AC XY:

10922

AN XY:

135400

show subpopulations

Gnomad AFR exome

AF:

0.0136

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.0542

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.0856

Gnomad FIN exome

AF:

0.118

Gnomad NFE exome

AF:

0.0897

Gnomad OTH exome

AF:

0.0841

GnomAD4 exome

AF:

0.0862

AC:

125966

AN:

1461762

Hom.:

5825

Cov.:

AF XY:

0.0863

AC XY:

62774

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.0121

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.0526

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.0852

Gnomad4 FIN exome

AF:

0.115

Gnomad4 NFE exome

AF:

0.0910

Gnomad4 OTH exome

AF:

0.0754

GnomAD4 genome

AF:

0.0683

AC:

10399

AN:

152322

Hom.:

508

Cov.:

AF XY:

0.0693

AC XY:

5160

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0164

Gnomad4 AMR

AF:

0.0925

Gnomad4 ASJ

AF:

0.0580

Gnomad4 EAS

AF:

0.000963

Gnomad4 SAS

AF:

0.0818

Gnomad4 FIN

AF:

0.114

Gnomad4 NFE

AF:

0.0917

Gnomad4 OTH

AF:

0.0596

Alfa

AF:

0.0816

Hom.:

191

Bravo

AF:

0.0641

TwinsUK

AF:

0.0947

AC:

351

ALSPAC

AF:

0.0911

AC:

351

ESP6500AA

AF:

0.0199

AC:

ESP6500EA

AF:

0.0879

AC:

734

ExAC

AF:

0.0801

AC:

9691

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.0868

EpiControl

AF:

0.0816

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

D;.

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.97

D;D

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-2.3

N;.

REVEL

Benign

0.20

Sift

Uncertain

0.016

D;.

Sift4G

Uncertain

0.030

D;T

Polyphen

0.62

P;.

Vest4

0.36

MPC

0.59

ClinPred

0.020

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.62

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over