11-31403056-T-G

Variant names:

• chr11-31403056-T-G
• rs6484503
• NM_181706.5:c.112-11755T>G

Variant summary

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

The NM_181706.5(DNAJC24):​c.112-11755T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,928 control chromosomes in the GnomAD database, including 11,841 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 0.39 (11841 hom., cov: 32)
• Consequence: DNAJC24 NM_181706.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC24	NM_181706.5	c.112-11755T>G		intron_variant	Intron 2 of 4	ENST00000465995.6	NP_859057.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC24	ENST00000465995.6	c.112-11755T>G		intron_variant	Intron 2 of 4	1	NM_181706.5	ENSP00000417548.1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58818 AN: 151810 Hom.: 11817 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.0713

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.388 AC: 58893 AN: 151928 Hom.: 11841 Cov.: 32 AF XY: 0.386 AC XY: 28662 AN XY: 74258

African (AFR) AF: 0.469 AC: 19386 AN: 41374

American (AMR) AF: 0.420 AC: 6412 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1443 AN: 3468

East Asian (EAS) AF: 0.0712 AC: 369 AN: 5180

South Asian (SAS) AF: 0.320 AC: 1543 AN: 4822

European-Finnish (FIN) AF: 0.386 AC: 4069 AN: 10540

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24299 AN: 67972

Other (OTH) AF: 0.389 AC: 820 AN: 2110

Alfa AF: 0.366 Hom.: 9853

Bravo AF: 0.396

Asia WGS AF: 0.195 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.4
DANN	Benign	0.76
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6484503; hg19: chr11-31424603;