8-66080396-G-T

Position:

• chr8-66080396-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_033105.6(DNAJC5B):​c.353G>T​(p.Gly118Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAJC5B NM_033105.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.42

Genes affected

DNAJC5B (HGNC:24138): (DnaJ heat shock protein family (Hsp40) member C5 beta) This gene encodes a member of the DNAJ heat shock protein 40 family of co-chaperone proteins that is characterized by an N-terminal DNAJ domain, a linker region, and a cysteine-rich C-terminal domain. The encoded protein, together with heat shock protein 70, is thought to regulate the proper folding of other proteins. The orthologous mouse protein is membrane-associated and is targeted to the trans-golgi network. [provided by RefSeq, Mar 2017]

DNAJC5B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.884

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC5B	NM_033105.6	c.353G>T	p.Gly118Val	missense_variant	5/6	ENST00000276570.10	NP_149096.2
DNAJC5B	NM_001349432.2	c.353G>T	p.Gly118Val	missense_variant	5/6		NP_001336361.1
DNAJC5B	XM_011517620.3	c.353G>T	p.Gly118Val	missense_variant	5/6		XP_011515922.1
DNAJC5B	NR_146171.2	n.2191G>T		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC5B	ENST00000276570.10	c.353G>T	p.Gly118Val	missense_variant	5/6	1	NM_033105.6	ENSP00000276570.5
DNAJC5B	ENST00000519330.1	n.2130G>T		non_coding_transcript_exon_variant	6/7	1
DNAJC5B	ENST00000524076.5	n.504G>T		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Feb 05, 2024

The c.353G>T (p.G118V) alteration is located in exon 5 (coding exon 3) of the DNAJC5B gene. This alteration results from a G to T substitution at nucleotide position 353, causing the glycine (G) at amino acid position 118 to be replaced by a valine (V). 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	0.21
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.056	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.61
Sift	Benign	0.030	D
Sift4G	Benign	0.13	T
Polyphen		0.38	B
Vest4		0.91
MutPred		0.71		Loss of loop (P = 0.0804);
MVP		0.90
MPC		0.54
ClinPred		0.97	D
GERP RS		5.9
Varity_R		0.46
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-66992631;