chr12-49349262-C-A

Position:

• chr12-49349262-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15859684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC22	NM_001304944.2	c.390C>A	p.Asp130Glu	missense_variant	3/4	ENST00000549441.7
DNAJC22	NM_024902.4	c.390C>A	p.Asp130Glu	missense_variant	2/3
DNAJC22	XM_047429555.1	c.390C>A	p.Asp130Glu	missense_variant	3/6
DNAJC22	XM_047429556.1	c.390C>A	p.Asp130Glu	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC22	ENST00000549441.7	c.390C>A	p.Asp130Glu	missense_variant	3/4	2	NM_001304944.2	P1
DNAJC22	ENST00000395069.3	c.390C>A	p.Asp130Glu	missense_variant	2/3	1		P1
DNAJC22	ENST00000647553.1	c.390C>A	p.Asp130Glu	missense_variant, NMD_transcript_variant	2/4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.390C>A (p.D130E) alteration is located in exon 2 (coding exon 1) of the DNAJC22 gene. This alteration results from a C to A substitution at nucleotide position 390, causing the aspartic acid (D) at amino acid position 130 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;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;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.4	M;M
MutationTaster	Benign	0.94	D;D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.68	N;N
REVEL	Benign	0.10
Sift	Benign	0.21	T;T
Sift4G	Uncertain	0.012	D;D
Polyphen		0.86	P;P
Vest4		0.45
MutPred		0.23		Gain of catalytic residue at Q127 (P = 8e-04);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs374090178; hg19: chr12-49743045;