9-34989820-A-C

Variant names:

• chr9-34989820-A-C
• NM_001349723.3:c.-144A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001349723.3(DNAJB5):​c.-144A>C 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. Variant has been reported in ClinVar as Uncertain significance (★).

• 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: 2.01
• Publications: 0 publications found

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]

DNAJB5-DT (HGNC:49846): (DNAJB5 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32795435).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349723.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB5	NM_001349723.3	MANE Select	c.-144A>C		5_prime_UTR	Exon 1 of 5	NP_001336652.1	O75953-4
	DNAJB5	NM_001135004.3		c.-89A>C		5_prime_UTR	Exon 1 of 5	NP_001128476.3	A0A7I2RN43
	DNAJB5	NM_001349725.2		c.-86A>C		5_prime_UTR	Exon 1 of 5	NP_001336654.2	A0A7I2RN43

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB5	ENST00000682809.1	MANE Select	c.-144A>C		5_prime_UTR	Exon 1 of 5	ENSP00000507741.1	O75953-4
	DNAJB5	ENST00000312316.9	TSL:1	c.-46A>C		5_prime_UTR	Exon 1 of 4	ENSP00000312517.5	O75953-3
	DNAJB5	ENST00000453597.8	TSL:2	c.-89A>C		5_prime_UTR	Exon 1 of 5	ENSP00000404079.4	A0A7I2RN43

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Benign	0.93
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.45	T
M_CAP	Pathogenic	0.94	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.57	T
PhyloP100		2.0
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.081
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.31
MutPred		0.27		Gain of glycosylation at Q51 (P = 0.002)
MVP		0.68
MPC		1.2
ClinPred		0.47	T
GERP RS		5.0
PromoterAI		0.034	Neutral
gMVP		0.50

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

Other links and lift over

hg19: chr9-34989817;