Genetic Variant DNAJB11:p.Ile17Ile (chr3-186570948-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP7

The NM_016306.6(DNAJB11):c.51C>A(p.Ile17Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000818 in 1,221,884 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I17I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 8.2e-7 ( 0 hom. )

Consequence

DNAJB11
NM_016306.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0510

Publications

0 publications found

Variant links:

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: ClinGen, Orphanet
polycystic kidney disease 6 with or without polycystic liver disease
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
ciliopathy
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

DNAJB11 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP7

Synonymous conserved (PhyloP=0.051 with no splicing effect.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAJB11	NM_016306.6	MANE Select	c.51C>A	p.Ile17Ile	synonymous	Exon 1 of 10	NP_057390.1	Q9UBS4
DNAJB11	NM_001378451.1		c.51C>A	p.Ile17Ile	synonymous	Exon 1 of 8	NP_001365380.1
DNAJB11	NR_165638.1		n.229C>A		non_coding_transcript_exon	Exon 1 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAJB11	ENST00000265028.8	TSL:1 MANE Select	c.51C>A	p.Ile17Ile	synonymous	Exon 1 of 10	ENSP00000265028.3	Q9UBS4
DNAJB11	ENST00000439351.5	TSL:1	c.51C>A	p.Ile17Ile	synonymous	Exon 2 of 11	ENSP00000414398.1	Q9UBS4
DNAJB11	ENST00000956498.1		c.51C>A	p.Ile17Ile	synonymous	Exon 1 of 10	ENSP00000626557.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.18e-7

AC:

AN:

1221884

Hom.:

Cov.:

AF XY:

0.00000165

AC XY:

AN XY:

604386

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26990

American (AMR)

AF:

0.00

AC:

AN:

35910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17434

East Asian (EAS)

AF:

0.00

AC:

AN:

17264

South Asian (SAS)

AF:

0.00

AC:

AN:

81302

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33846

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4588

European-Non Finnish (NFE)

AF:

0.00000104

AC:

AN:

959402

Other (OTH)

AF:

0.00

AC:

AN:

45148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

0.051

PromoterAI

-0.044

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over