3-186572127-G-A

Position:

• chr3-186572127-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016306.6(DNAJB11):​c.101G>A​(p.Arg34Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000207 in 1,449,002 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: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DNAJB11 NM_016306.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.51

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32024944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJB11	NM_016306.6	c.101G>A	p.Arg34Gln	missense_variant	2/10	ENST00000265028.8	NP_057390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJB11	ENST00000265028.8	c.101G>A	p.Arg34Gln	missense_variant	2/10	1	NM_016306.6	ENSP00000265028.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000416 AC: 1 AN: 240670 Hom.: 0 AF XY: 0.00000769 AC XY: 1 AN XY: 130106

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000571

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1449002 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2 AN XY: 720758

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.78	.;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.18
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.023	D;D
Polyphen		0.99	D;D
Vest4		0.30
MutPred		0.60		Gain of glycosylation at S37 (P = 0.0135);Gain of glycosylation at S37 (P = 0.0135);
MVP		0.52
MPC		0.70
ClinPred		0.74	D
GERP RS		5.4
Varity_R		0.16
gMVP		0.15

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: rs1431484336; hg19: chr3-186289916; COSMIC: COSV54003617; COSMIC: COSV54003617;