9-34989762-C-T

Variant names:

• chr9-34989762-C-T
• rs924152311
• NM_001349723.3:c.-202C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001349723.3(DNAJB5):​c.-202C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000487 in 1,231,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: DNAJB5 NM_001349723.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92
• Publications: 1 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25381708).

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.-202C>T		5_prime_UTR	Exon 1 of 5	NP_001336652.1	O75953-4
	DNAJB5	NM_001135004.3		c.-147C>T		5_prime_UTR	Exon 1 of 5	NP_001128476.3	A0A7I2RN43
	DNAJB5	NM_001349725.2		c.-144C>T		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.-202C>T		5_prime_UTR	Exon 1 of 5	ENSP00000507741.1	O75953-4
	DNAJB5	ENST00000312316.9	TSL:1	c.-104C>T		5_prime_UTR	Exon 1 of 4	ENSP00000312517.5	O75953-3
	DNAJB5	ENST00000453597.8	TSL:2	c.-147C>T		5_prime_UTR	Exon 1 of 5	ENSP00000404079.4	A0A7I2RN43

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152124 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: 0.000386

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000278 AC: 3 AN: 1079094 Hom.: 0 Cov.: 30 AF XY: 0.00000196 AC XY: 1 AN XY: 509490

African (AFR) AF: 0.00 AC: 0 AN: 22930

American (AMR) AF: 0.00 AC: 0 AN: 8388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14350

East Asian (EAS) AF: 0.0000755 AC: 2 AN: 26498

South Asian (SAS) AF: 0.00 AC: 0 AN: 19666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2914

European-Non Finnish (NFE) AF: 0.00000109 AC: 1 AN: 919612

Other (OTH) AF: 0.00 AC: 0 AN: 43630

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152124 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74324

African (AFR) AF: 0.00 AC: 0 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

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	0.21
BayesDel_addAF	Benign	0.0091	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Benign	0.96
Eigen	Benign	0.17
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.61	T
M_CAP	Pathogenic	0.81	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.66	T
PhyloP100		1.9
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.032
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.28
MutPred		0.27		Loss of methylation at R32 (P = 0.0375)
MVP		0.66
MPC		1.0
ClinPred		0.63	D
GERP RS		3.1
PromoterAI		-0.069	Neutral
gMVP		0.17

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: rs924152311; hg19: chr9-34989759;