rs483534

Variant names:

• chr11-31376595-C-G
• rs483534
• NM_181706.5:c.111+5736C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-31376595-C-G
• chr11-31376595-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181706.5(DNAJC24):​c.111+5736C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,000 control chromosomes in the GnomAD database, including 14,388 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 0.42 (14388 hom., cov: 32)
• Consequence: DNAJC24 NM_181706.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181706.5. 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
	DNAJC24	NM_181706.5	MANE Select	c.111+5736C>G		intron	N/A	NP_859057.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC24	ENST00000465995.6	TSL:1 MANE Select	c.111+5736C>G		intron	N/A	ENSP00000417548.1	Q6P3W2-1
	DNAJC24	ENST00000526042.5	TSL:1	n.111+5736C>G		intron	N/A	ENSP00000435771.1	Q6P3W2-2
	DNAJC24	ENST00000910453.1		c.111+5736C>G		intron	N/A	ENSP00000580512.1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63686 AN: 151882 Hom.: 14351 Cov.: 32

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.0712

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.420 AC: 63778 AN: 152000 Hom.: 14388 Cov.: 32 AF XY: 0.417 AC XY: 30959 AN XY: 74308

African (AFR) AF: 0.580 AC: 24019 AN: 41446

American (AMR) AF: 0.434 AC: 6625 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1439 AN: 3468

East Asian (EAS) AF: 0.0711 AC: 369 AN: 5188

South Asian (SAS) AF: 0.317 AC: 1529 AN: 4822

European-Finnish (FIN) AF: 0.384 AC: 4053 AN: 10550

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.358 AC: 24317 AN: 67936

Other (OTH) AF: 0.416 AC: 876 AN: 2108

Alfa AF: 0.227 Hom.: 466

Bravo AF: 0.433

Asia WGS AF: 0.204 AC: 713 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.0
DANN	Benign	0.83
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs483534; hg19: chr11-31398142;