12-49349315-G-T

Position:

• chr12-49349315-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001304944.2(DNAJC22):​c.443G>T​(p.Arg148Leu) 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. 13/21 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: 2.79

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31907845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC22	NM_001304944.2	c.443G>T	p.Arg148Leu	missense_variant	3/4	ENST00000549441.7	NP_001291873.1
DNAJC22	NM_024902.4	c.443G>T	p.Arg148Leu	missense_variant	2/3		NP_079178.2
DNAJC22	XM_047429555.1	c.443G>T	p.Arg148Leu	missense_variant	3/6		XP_047285511.1
DNAJC22	XM_047429556.1	c.443G>T	p.Arg148Leu	missense_variant	3/5		XP_047285512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC22	ENST00000549441.7	c.443G>T	p.Arg148Leu	missense_variant	3/4	2	NM_001304944.2	ENSP00000446830.1
DNAJC22	ENST00000395069.3	c.443G>T	p.Arg148Leu	missense_variant	2/3	1		ENSP00000378508.2
DNAJC22	ENST00000647553.1	n.443G>T		non_coding_transcript_exon_variant	2/4			ENSP00000498036.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Nov 12, 2021

The c.443G>T (p.R148L) alteration is located in exon 2 (coding exon 1) of the DNAJC22 gene. This alteration results from a G to T substitution at nucleotide position 443, causing the arginine (R) at amino acid position 148 to be replaced by a leucine (L). 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	Benign	0.19
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T;T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.072
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.16
Sift	Benign	0.063	T;T
Sift4G	Uncertain	0.025	D;D
Polyphen		0.42	B;B
Vest4		0.47
MutPred		0.51		Gain of catalytic residue at R148 (P = 0);Gain of catalytic residue at R148 (P = 0);
MVP		0.56
MPC		0.057
ClinPred		0.92	D
GERP RS		2.0
Varity_R		0.20
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-49743098;