3-186572080-C-T

Variant names:

• chr3-186572080-C-T
• rs757507181
• NM_016306.6:c.69-15C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_016306.6(DNAJB11):​c.69-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,402,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: DNAJB11 NM_016306.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.55
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant polycystic kidney disease

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• polycystic kidney disease 6 with or without polycystic liver disease

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• ciliopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 3-186572080-C-T is Benign according to our data. Variant chr3-186572080-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2760738.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016306.6. 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
	DNAJB11	NM_016306.6	MANE Select	c.69-15C>T		intron	N/A	NP_057390.1	Q9UBS4
	DNAJB11	NM_001378451.1		c.69-15C>T		intron	N/A	NP_001365380.1
	DNAJB11	NR_165638.1		n.247-15C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB11	ENST00000265028.8	TSL:1 MANE Select	c.69-15C>T		intron	N/A	ENSP00000265028.3	Q9UBS4
	DNAJB11	ENST00000439351.5	TSL:1	c.69-15C>T		intron	N/A	ENSP00000414398.1	Q9UBS4
	DNAJB11	ENST00000956498.1		c.69-15C>T		intron	N/A	ENSP00000626557.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1402584 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 696434

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30622

American (AMR) AF: 0.00 AC: 0 AN: 30954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23178

East Asian (EAS) AF: 0.00 AC: 0 AN: 38944

South Asian (SAS) AF: 0.00 AC: 0 AN: 77196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5490

European-Non Finnish (NFE) AF: 9.20e-7 AC: 1 AN: 1086738

Other (OTH) AF: 0.00 AC: 0 AN: 57572

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.75
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs757507181; hg19: chr3-186289869;