3-186570629-C-T

Position:

• chr3-186570629-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000439351(DNAJB11):​c.-269C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00777 in 568,642 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (111 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (27 hom.)
• Consequence: DNAJB11 ENST00000439351 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.292

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 3-186570629-C-T is Benign according to our data. Variant chr3-186570629-C-T is described in ClinVar as [Benign]. Clinvar id is 1227060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.186570629C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJB11	ENST00000439351	c.-269C>T		5_prime_UTR_variant	2/11	1		ENSP00000414398.1

Frequencies

GnomAD3 genomes AF: 0.0213 AC: 3248 AN: 152186 Hom.: 110 Cov.: 32

Gnomad AFR AF: 0.0740

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00785

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.00277 AC: 1155 AN: 416338 Hom.: 27 Cov.: 0 AF XY: 0.00236 AC XY: 520 AN XY: 220178

Gnomad4 AFR exome AF: 0.0757

Gnomad4 AMR exome AF: 0.00817

Gnomad4 ASJ exome AF: 0.00202

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000188

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000309

Gnomad4 OTH exome AF: 0.00526

GnomAD4 genome AF: 0.0214 AC: 3263 AN: 152304 Hom.: 111 Cov.: 32 AF XY: 0.0205 AC XY: 1524 AN XY: 74464

Gnomad4 AFR AF: 0.0741

Gnomad4 AMR AF: 0.00784

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.0156 Hom.: 10

Bravo AF: 0.0246

Asia WGS AF: 0.00289 AC: 10 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 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Benign	0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs114104753; hg19: chr3-186288418;