chr3-186570776-A-G

Position:

• chr3-186570776-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016306.6(DNAJB11):​c.-122A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 861,524 control chromosomes in the GnomAD database, including 297,791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (47406 hom., cov: 31)
  • Exomes 𝑓: 0.84 (250385 hom.)
• Consequence: DNAJB11 NM_016306.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.39

Genes affected

DNAJB11 (HGNC:14889): (DnaJ heat shock protein family (Hsp40) member B11) This gene encodes a soluble glycoprotein of the endoplasmic reticulum (ER) lumen that functions as a co-chaperone of binding immunoglobulin protein, a 70 kilodalton heat shock protein chaperone required for the proper folding and assembly of proteins in the ER. The encoded protein contains a highly conserved J domain of about 70 amino acids with a characteristic His-Pro-Asp (HPD) motif and may regulate the activity of binding immunoglobulin protein by stimulating ATPase activity. [provided by RefSeq, Mar 2014]

DNAJB11 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 3-186570776-A-G is Benign according to our data. Variant chr3-186570776-A-G is described in ClinVar as [Benign]. Clinvar id is 1294633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJB11	NM_016306.6	c.-122A>G		5_prime_UTR_variant	1/10	ENST00000265028.8	NP_057390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJB11	ENST00000265028	c.-122A>G		5_prime_UTR_variant	1/10	1	NM_016306.6	ENSP00000265028.3

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119214 AN: 151958 Hom.: 47377 Cov.: 31

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.830

GnomAD4 exome AF: 0.839 AC: 594931 AN: 709448 Hom.: 250385 Cov.: 9 AF XY: 0.841 AC XY: 313247 AN XY: 372390

Gnomad4 AFR exome AF: 0.643

Gnomad4 AMR exome AF: 0.893

Gnomad4 ASJ exome AF: 0.909

Gnomad4 EAS exome AF: 0.915

Gnomad4 SAS exome AF: 0.885

Gnomad4 FIN exome AF: 0.797

Gnomad4 NFE exome AF: 0.832

Gnomad4 OTH exome AF: 0.839

GnomAD4 genome AF: 0.784 AC: 119284 AN: 152076 Hom.: 47406 Cov.: 31 AF XY: 0.787 AC XY: 58510 AN XY: 74346

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.866

Gnomad4 ASJ AF: 0.910

Gnomad4 EAS AF: 0.901

Gnomad4 SAS AF: 0.881

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.829

Gnomad4 OTH AF: 0.831

Alfa AF: 0.832 Hom.: 44081

Bravo AF: 0.784

Asia WGS AF: 0.857 AC: 2981 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.4
DANN	Benign	0.74

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: rs3806714; hg19: chr3-186288565;