chr12-49349262-C-A

Variant names:

• chr12-49349262-C-A
• rs374090178
• NM_001304944.2:c.390C>A

Variant summary

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

The NM_001304944.2(DNAJC22):​c.390C>A​(p.Asp130Glu) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D130H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAJC22 NM_001304944.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0430
• Publications: 0 publications found

Genes affected

DNAJC22 (HGNC:25802): (DnaJ heat shock protein family (Hsp40) member C22) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.15859684).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304944.2. 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
	DNAJC22	NM_001304944.2	MANE Select	c.390C>A	p.Asp130Glu	missense	Exon 3 of 4	NP_001291873.1	Q8N4W6
	DNAJC22	NM_024902.4		c.390C>A	p.Asp130Glu	missense	Exon 2 of 3	NP_079178.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC22	ENST00000549441.7	TSL:2 MANE Select	c.390C>A	p.Asp130Glu	missense	Exon 3 of 4	ENSP00000446830.1	Q8N4W6
	DNAJC22	ENST00000395069.3	TSL:1	c.390C>A	p.Asp130Glu	missense	Exon 2 of 3	ENSP00000378508.2	Q8N4W6
	DNAJC22	ENST00000851339.1		c.390C>A	p.Asp130Glu	missense	Exon 4 of 5	ENSP00000521398.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	0.39
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T
Eigen	Benign	0.0090
Eigen_PC	Benign	-0.037
FATHMM_MKL	Benign	0.48	N
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.043
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.10
Sift	Benign	0.21	T
Sift4G	Uncertain	0.012	D
Polyphen		0.86	P
Vest4		0.45
MutPred		0.23		Gain of catalytic residue at Q127 (P = 8e-04)
MVP		0.30
MPC		0.037
ClinPred		0.83	D
GERP RS		3.0
Varity_R		0.095
gMVP		0.56
Mutation Taster		=91/9	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: rs374090178; hg19: chr12-49743045;