9-34989804-C-G

Variant names:

• chr9-34989804-C-G
• rs1827567989
• NM_001349723.3:c.-160C>G

Variant summary

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

The NM_001349723.3(DNAJB5):​c.-160C>G variant causes a 5 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAJB5 NM_001349723.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45

Genes affected

DNAJB5 (HGNC:14887): (DnaJ heat shock protein family (Hsp40) member B5) This gene encodes a member of the DNAJ heat shock protein 40 family of co-chaperone proteins. The encoded protein contains an N-terminal DNAJ domain and a C-terminal substrate binding domain but lacks the cysteine-rich domain found in other DNAJ family members. In mice, a multi-protein complex containing this protein, thioredoxin 1, and histone deacetylase 4, serves as a master negative regulator of cardiac hypertrophy. [provided by RefSeq, Mar 2017]

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=0.37165076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJB5	NM_001349723.3	c.-160C>G		5_prime_UTR_variant	Exon 1 of 5	ENST00000682809.1	NP_001336652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJB5	ENST00000682809	c.-160C>G		5_prime_UTR_variant	Exon 1 of 5		NM_001349723.3	ENSP00000507741.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.136C>G (p.P46A) alteration is located in exon 1 (coding exon 1) of the DNAJB5 gene. This alteration results from a C to G substitution at nucleotide position 136, causing the proline (P) at amino acid position 46 to be replaced by an alanine (A). 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
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Benign	0.92
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.55	T
M_CAP	Pathogenic	0.89	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.75	T
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.023
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.35
MutPred		0.24		Loss of glycosylation at P46 (P = 0.0078);
MVP		0.67
MPC		0.97
ClinPred		0.78	D
GERP RS		4.1
gMVP		0.10

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: rs1827567989; hg19: chr9-34989801;