NM_018981.4:c.1066A>G

Variant names:

• chr2-182740377-A-G
• rs200062649
• NM_018981.4:c.1066A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018981.4(DNAJC10):​c.1066A>G​(p.Asn356Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N356Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAJC10 NM_018981.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.979
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034195125).

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.1066A>G	p.Asn356Asp	missense	Exon 12 of 24	NP_061854.1	Q8IXB1-1
	DNAJC10	NM_001271581.3		c.928A>G	p.Asn310Asp	missense	Exon 11 of 23	NP_001258510.1	Q8IXB1-2
	DNAJC10	NR_073365.2		n.2250A>G		non_coding_transcript_exon	Exon 12 of 24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC10	ENST00000264065.12	TSL:1 MANE Select	c.1066A>G	p.Asn356Asp	missense	Exon 12 of 24	ENSP00000264065.6	Q8IXB1-1
	DNAJC10	ENST00000616986.5	TSL:1	c.928A>G	p.Asn310Asp	missense	Exon 11 of 23	ENSP00000479930.1	Q8IXB1-2
	DNAJC10	ENST00000418559.6	TSL:1	n.*56A>G		non_coding_transcript_exon	Exon 8 of 21	ENSP00000389483.1	E7EP04

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.7
DANN	Benign	0.43
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		0.98
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.51	N
REVEL	Benign	0.026
Sift	Benign	0.68	T
Sift4G	Benign	0.69	T
Polyphen		0.0	B
Vest4		0.098
MutPred		0.31		Loss of stability (P = 0.0776)
MVP		0.17
MPC		0.071
ClinPred		0.054	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.020
gMVP		0.34
Mutation Taster		=96/4	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: rs200062649; hg19: chr2-183605104;