chr9-34989804-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 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: 2.45
• 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=0.37165076).

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.-160C>G		5_prime_UTR	Exon 1 of 5	NP_001336652.1	O75953-4
	DNAJB5	NM_001135004.3		c.-105C>G		5_prime_UTR	Exon 1 of 5	NP_001128476.3	A0A7I2RN43
	DNAJB5	NM_001349725.2		c.-102C>G		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.-160C>G		5_prime_UTR	Exon 1 of 5	ENSP00000507741.1	O75953-4
	DNAJB5	ENST00000312316.9	TSL:1	c.-62C>G		5_prime_UTR	Exon 1 of 4	ENSP00000312517.5	O75953-3
	DNAJB5	ENST00000453597.8	TSL:2	c.-105C>G		5_prime_UTR	Exon 1 of 5	ENSP00000404079.4	A0A7I2RN43

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.064
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
PhyloP100		2.5
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
PromoterAI		-0.062	Neutral
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

Other links and lift over

dbSNP: rs1827567989; hg19: chr9-34989801;