9-34989811-G-A

Variant names:

• chr9-34989811-G-A
• rs945699372
• NM_001349723.3:c.-153G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001349723.3(DNAJB5):​c.-153G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00027 in 1,232,258 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (3 hom.)
• Consequence: DNAJB5 NM_001349723.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.626
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2606666).
• BS2: High AC in GnomAd4 at 13 AD gene.

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.-153G>A		5_prime_UTR	Exon 1 of 5	NP_001336652.1	O75953-4
	DNAJB5	NM_001135004.3		c.-98G>A		5_prime_UTR	Exon 1 of 5	NP_001128476.3	A0A7I2RN43
	DNAJB5	NM_001349725.2		c.-95G>A		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.-153G>A		5_prime_UTR	Exon 1 of 5	ENSP00000507741.1	O75953-4
	DNAJB5	ENST00000312316.9	TSL:1	c.-55G>A		5_prime_UTR	Exon 1 of 4	ENSP00000312517.5	O75953-3
	DNAJB5	ENST00000453597.8	TSL:2	c.-98G>A		5_prime_UTR	Exon 1 of 5	ENSP00000404079.4	A0A7I2RN43

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000296 AC: 320 AN: 1079994 Hom.: 3 Cov.: 30 AF XY: 0.000296 AC XY: 151 AN XY: 510006

African (AFR) AF: 0.00 AC: 0 AN: 22926

American (AMR) AF: 0.00 AC: 0 AN: 8520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14354

East Asian (EAS) AF: 0.0120 AC: 317 AN: 26496

South Asian (SAS) AF: 0.00 AC: 0 AN: 19838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2916

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 920170

Other (OTH) AF: 0.0000687 AC: 3 AN: 43656

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152264 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74434

African (AFR) AF: 0.00 AC: 0 AN: 41560

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00252 AC: 13 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

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	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Uncertain	0.98
Eigen	Benign	-0.071
Eigen_PC	Benign	-0.040
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.53	T
M_CAP	Pathogenic	0.89	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.75	T
PhyloP100		0.63
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.026
Sift	Benign	0.13	T
Sift4G	Benign	0.42	T
Vest4		0.15
MutPred		0.28		Gain of loop (P = 0.0195)
MVP		0.68
MPC		1.1
ClinPred		0.22	T
GERP RS		3.2
PromoterAI		-0.055	Neutral
gMVP		0.057

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: rs945699372; hg19: chr9-34989808;