chr10-21882431-T-C

Variant names:

• chr10-21882431-T-C
• NM_022365.4:c.829A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022365.4(DNAJC1):​c.829A>G​(p.Lys277Glu) 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. 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: 4.41
• Publications: 0 publications found

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

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3563272).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022365.4. 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
	DNAJC1	NM_022365.4	MANE Select	c.829A>G	p.Lys277Glu	missense	Exon 8 of 12	NP_071760.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC1	ENST00000376980.8	TSL:1 MANE Select	c.829A>G	p.Lys277Glu	missense	Exon 8 of 12	ENSP00000366179.3	Q96KC8
	DNAJC1	ENST00000883425.1		c.829A>G	p.Lys277Glu	missense	Exon 8 of 13	ENSP00000553484.1
	DNAJC1	ENST00000963964.1		c.829A>G	p.Lys277Glu	missense	Exon 8 of 12	ENSP00000634023.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.4
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.21
Sift	Benign	0.086	T
Sift4G	Uncertain	0.013	D
Polyphen		0.95	P
Vest4		0.47
MutPred		0.23		Loss of methylation at K277 (P = 0.0048)
MVP		0.78
MPC		0.86
ClinPred		0.85	D
GERP RS		6.0
Varity_R		0.28
gMVP		0.53
Mutation Taster		=39/61	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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

hg19: chr10-22171360;