9-34996285-A-T

Variant names:

• chr9-34996285-A-T
• rs1384468289
• NM_001349723.3:c.448A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001349723.3(DNAJB5):​c.448A>T​(p.Thr150Ser) variant causes a missense 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. 17/22 in silico tools predict 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 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.330
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.017093211).

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.448A>T	p.Thr150Ser	missense	Exon 4 of 5	NP_001336652.1	O75953-4
	DNAJB5	NM_001135005.3		c.448A>T	p.Thr150Ser	missense	Exon 3 of 4	NP_001128477.1	O75953-4
	DNAJB5	NM_001135004.3		c.334A>T	p.Thr112Ser	missense	Exon 4 of 5	NP_001128476.3	A0A7I2RN43

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB5	ENST00000682809.1	MANE Select	c.448A>T	p.Thr150Ser	missense	Exon 4 of 5	ENSP00000507741.1	O75953-4
	DNAJB5	ENST00000454002.6	TSL:1	c.448A>T	p.Thr150Ser	missense	Exon 3 of 4	ENSP00000413684.2	O75953-4
	DNAJB5	ENST00000312316.9	TSL:1	c.232A>T	p.Thr78Ser	missense	Exon 3 of 4	ENSP00000312517.5	O75953-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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 provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.30
DANN	Benign	0.13
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.47	N
PhyloP100		0.33
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.99	N
REVEL	Benign	0.049
Sift	Benign	1.0	T
Sift4G	Benign	0.86	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.31		Gain of phosphorylation at T78 (P = 0.0588)
MVP		0.60
MPC		0.90
ClinPred		0.019	T
GERP RS		-0.038
Varity_R		0.033
gMVP		0.38
Mutation Taster		=93/7	polymorphism

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: rs1384468289; hg19: chr9-34996282;