NM_016306.6:c.98C>T

Variant names:

• chr3-186572124-C-T
• rs1715084223
• NM_016306.6:c.98C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016306.6(DNAJB11):​c.98C>T​(p.Pro33Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,449,474 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DNAJB11 NM_016306.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.11
• 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: 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25728434).

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.98C>T	p.Pro33Leu	missense	Exon 2 of 10	NP_057390.1	Q9UBS4
	DNAJB11	NM_001378451.1		c.98C>T	p.Pro33Leu	missense	Exon 2 of 8	NP_001365380.1
	DNAJB11	NR_165638.1		n.276C>T		non_coding_transcript_exon	Exon 2 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB11	ENST00000265028.8	TSL:1 MANE Select	c.98C>T	p.Pro33Leu	missense	Exon 2 of 10	ENSP00000265028.3	Q9UBS4
	DNAJB11	ENST00000439351.5	TSL:1	c.98C>T	p.Pro33Leu	missense	Exon 3 of 11	ENSP00000414398.1	Q9UBS4
	DNAJB11	ENST00000956498.1		c.98C>T	p.Pro33Leu	missense	Exon 2 of 10	ENSP00000626557.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449474 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 720916

African (AFR) AF: 0.00 AC: 0 AN: 32648

American (AMR) AF: 0.00 AC: 0 AN: 41824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25628

East Asian (EAS) AF: 0.00 AC: 0 AN: 39536

South Asian (SAS) AF: 0.00 AC: 0 AN: 83394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107788

Other (OTH) AF: 0.00 AC: 0 AN: 59756

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.1
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.29
Sift	Benign	0.030	D
Sift4G	Benign	0.16	T
Polyphen		0.0060	B
Vest4		0.26
MutPred		0.52		Gain of glycosylation at S37 (P = 0.0135)
MVP		0.47
MPC		0.62
ClinPred		0.93	D
GERP RS		5.4
Varity_R		0.23
gMVP		0.41
Mutation Taster		=94/6	polymorphism

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: rs1715084223; hg19: chr3-186289913;