rs578666

chr11-31382937-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181706.5(DNAJC24):c.111+12078G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 152,012 control chromosomes in the GnomAD database, including 39,452 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 0.71 (39452 hom., cov: 32)
• Consequence: DNAJC24 NM_181706.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

Genes affected

DNAJC24 (HGNC:26979): (DnaJ heat shock protein family (Hsp40) member C24) Diphthamide is a unique posttranslationally modified histidine found only in translation elongation factor-2 (EEF2; MIM 130610). This modification is conserved from archaebacteria to humans and serves as the target for ADP-ribosylation and inactivation of EEF2 by diphtheria toxin (DT) and Pseudomonas exotoxin A. DPH4 is 1 of several enzymes involved in synthesis of diphthamide in EEF2 (Liu et al., 2004 [PubMed 15485916]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC24	NM_181706.5	c.111+12078G>A		intron_variant		ENST00000465995.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC24	ENST00000465995.6	c.111+12078G>A		intron_variant		1	NM_181706.5	P1

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107370 AN: 151894 Hom.: 39389 Cov.: 32

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.720

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.707 AC: 107498 AN: 152012 Hom.: 39452 Cov.: 32 AF XY: 0.698 AC XY: 51866 AN XY: 74294

Gnomad4 AFR AF: 0.901

Gnomad4 AMR AF: 0.717

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.643

Gnomad4 OTH AF: 0.723

Alfa AF: 0.649 Hom.: 35302

Bravo AF: 0.730

Asia WGS AF: 0.545 AC: 1899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.93
Dann	Benign	0.35

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

Other links and lift over

dbSNP: rs578666; hg19: chr11-31404484;