2-182741255-C-A

Variant names:

• chr2-182741255-C-A
• rs138024183
• NM_018981.4:c.1090C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018981.4(DNAJC10):​c.1090C>A​(p.His364Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,449,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. H364Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DNAJC10 NM_018981.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.95
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24138665).

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.1090C>A	p.His364Asn	missense	Exon 13 of 24	NP_061854.1	Q8IXB1-1
	DNAJC10	NM_001271581.3		c.952C>A	p.His318Asn	missense	Exon 12 of 23	NP_001258510.1	Q8IXB1-2
	DNAJC10	NR_073365.2		n.2274C>A		non_coding_transcript_exon	Exon 13 of 24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC10	ENST00000264065.12	TSL:1 MANE Select	c.1090C>A	p.His364Asn	missense	Exon 13 of 24	ENSP00000264065.6	Q8IXB1-1
	DNAJC10	ENST00000616986.5	TSL:1	c.952C>A	p.His318Asn	missense	Exon 12 of 23	ENSP00000479930.1	Q8IXB1-2
	DNAJC10	ENST00000418559.6	TSL:1	n.*80C>A		non_coding_transcript_exon	Exon 9 of 21	ENSP00000389483.1	E7EP04

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1449090 Hom.: 0 Cov.: 28 AF XY: 0.00000277 AC XY: 2 AN XY: 720752

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32584

American (AMR) AF: 0.00 AC: 0 AN: 42884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25928

East Asian (EAS) AF: 0.00 AC: 0 AN: 39000

South Asian (SAS) AF: 0.00 AC: 0 AN: 83574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106296

Other (OTH) AF: 0.0000167 AC: 1 AN: 59892

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.0063	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.9
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.095
Sift	Benign	0.30	T
Sift4G	Benign	0.92	T
Polyphen		0.47	P
Vest4		0.50
MutPred		0.36		Loss of helix (P = 0.1299)
MVP		0.30
MPC		0.19
ClinPred		0.92	D
GERP RS		4.8
Varity_R		0.19
gMVP		0.63
Mutation Taster		=59/41	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: rs138024183; hg19: chr2-183605982;