10-21904534-C-G

Position:

• chr10-21904534-C-G

Variant summary

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

The NM_022365.4(DNAJC1):​c.808G>C​(p.Glu270Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DNAJC1 NM_022365.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.41

Genes affected

DNAJC1 (HGNC:20090): (DnaJ heat shock protein family (Hsp40) member C1) The membrane protein encoded by this gene is a DNAJ-like heat shock protein that binds the molecular chaperone BiP. In addition, the encoded protein contains two SANT domains that have been shown to bind serpin alpha1-antichymotrypsin and inter-alpha trypsin inhibitor heavy chain 4. [provided by RefSeq, Jul 2016]

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=0.4114509).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC1	NM_022365.4	c.808G>C	p.Glu270Gln	missense_variant	7/12	ENST00000376980.8	NP_071760.2
DNAJC1	XM_011519614.4	c.808G>C	p.Glu270Gln	missense_variant	7/10		XP_011517916.1
DNAJC1	XM_017016536.3	c.808G>C	p.Glu270Gln	missense_variant	7/9		XP_016872025.1
DNAJC1	XM_047425628.1	c.808G>C	p.Glu270Gln	missense_variant	7/10		XP_047281584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC1	ENST00000376980.8	c.808G>C	p.Glu270Gln	missense_variant	7/12	1	NM_022365.4	ENSP00000366179	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 22, 2023

The c.808G>C (p.E270Q) alteration is located in exon 7 (coding exon 7) of the DNAJC1 gene. This alteration results from a G to C substitution at nucleotide position 808, causing the glutamic acid (E) at amino acid position 270 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.0047	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.091	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.12
Sift	Benign	0.049	D
Sift4G	Uncertain	0.019	D
Polyphen		0.18	B
Vest4		0.56
MutPred		0.17		Gain of MoRF binding (P = 0.0221);
MVP		0.65
MPC		0.28
ClinPred		0.82	D
GERP RS		5.7
Varity_R		0.30
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-22193463;