15-78264847-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001130182.2(DNAJA4):c.84G>C(p.Lys28Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DNAJA4 NM_001130182.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.778

Genes affected

DNAJA4 (HGNC:14885): (DnaJ heat shock protein family (Hsp40) member A4) Enables chaperone binding activity and unfolded protein binding activity. Involved in several processes, including negative regulation of endothelial cell migration; negative regulation of inclusion body assembly; and protein refolding. Located in cytosol and membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJA4	NM_001130182.2	c.84G>C	p.Lys28Asn	missense_variant	1/7	ENST00000394852.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJA4	ENST00000394852.8	c.84G>C	p.Lys28Asn	missense_variant	1/7	1	NM_001130182.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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

May 09, 2022

The c.171G>C (p.K57N) alteration is located in exon 2 (coding exon 2) of the DNAJA4 gene. This alteration results from a G to C substitution at nucleotide position 171, causing the lysine (K) at amino acid position 57 to be replaced by an asparagine (N). 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	Pathogenic	0.95
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
Cadd	Uncertain	24
Dann	Uncertain	0.99
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.82	T;T;.;T
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.50	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-4.2	D;D;D;D
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		0.54	P;.;B;B
Vest4		0.52
MutPred		0.70		.;.;Loss of methylation at K28 (P = 0.0132);Loss of methylation at K28 (P = 0.0132);
MVP		0.42
MPC		0.67
ClinPred		1.0	D
GERP RS		-1.4
Varity_R		0.84
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr15-78557189;