NM_018981.4:c.205A>C

Variant names:

• chr2-182720007-A-C
• NM_018981.4:c.205A>C

Variant summary

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

The NM_018981.4(DNAJC10):​c.205A>C​(p.Asn69His) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: DNAJC10 NM_018981.4 missense, splice_region
• Scores: Splicing: ADA: 0.8025
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.11
• Publications: 0 publications found

Genes affected

DNAJC10 (HGNC:24637): (DnaJ heat shock protein family (Hsp40) member C10) This gene encodes an endoplasmic reticulum co-chaperone which is part of the endoplasmic reticulum-associated degradation complex involved in recognizing and degrading misfolded proteins. The encoded protein reduces incorrect disulfide bonds in misfolded glycoproteins. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

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=0.37266955).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018981.4. 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
	DNAJC10	NM_018981.4	MANE Select	c.205A>C	p.Asn69His	missense splice_region	Exon 4 of 24	NP_061854.1	Q8IXB1-1
	DNAJC10	NM_001271581.3		c.205A>C	p.Asn69His	missense splice_region	Exon 4 of 23	NP_001258510.1	Q8IXB1-2
	DNAJC10	NR_073365.2		n.635A>C		splice_region non_coding_transcript_exon	Exon 4 of 24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC10	ENST00000264065.12	TSL:1 MANE Select	c.205A>C	p.Asn69His	missense splice_region	Exon 4 of 24	ENSP00000264065.6	Q8IXB1-1
	DNAJC10	ENST00000616986.5	TSL:1	c.205A>C	p.Asn69His	missense splice_region	Exon 4 of 23	ENSP00000479930.1	Q8IXB1-2
	DNAJC10	ENST00000537515.5	TSL:1	c.205A>C	p.Asn69His	missense splice_region	Exon 2 of 10	ENSP00000441560.1	Q8IXB1-3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 22

GnomAD4 genome Cov.: 30

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	Benign	0.10
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	0.67	N
PhyloP100		5.1
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.027	D
Polyphen		0.98	D
Vest4		0.39
MutPred		0.44		Gain of catalytic residue at N70 (P = 0.1296)
MVP		0.86
MPC		0.10
ClinPred		0.75	D
GERP RS		5.7
Varity_R		0.19
gMVP		0.34
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.80
dbscSNV1_RF	Benign	0.52
SpliceAI score (max)		0.070		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: chr2-183584734;