9-34990700-C-A

Variant names:

• chr9-34990700-C-A
• rs1827603267
• NM_001349723.3:c.70C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001349723.3(DNAJB5):​c.70C>A​(p.Arg24Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: DNAJB5 NM_001349723.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=1.38 with no splicing effect.

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.70C>A	p.Arg24Arg	synonymous	Exon 2 of 5	NP_001336652.1	O75953-4
	DNAJB5	NM_001135005.3		c.70C>A	p.Arg24Arg	synonymous	Exon 1 of 4	NP_001128477.1	O75953-4
	DNAJB5	NM_001135004.3		c.-45C>A		5_prime_UTR	Exon 2 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.70C>A	p.Arg24Arg	synonymous	Exon 2 of 5	ENSP00000507741.1	O75953-4
	DNAJB5	ENST00000454002.6	TSL:1	c.70C>A	p.Arg24Arg	synonymous	Exon 1 of 4	ENSP00000413684.2	O75953-4
	DNAJB5	ENST00000312316.9	TSL:1	c.-35+869C>A		intron	N/A	ENSP00000312517.5	O75953-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399414 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690216

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078972

Other (OTH) AF: 0.00 AC: 0 AN: 58002

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.64
PhyloP100		1.4
PromoterAI		-0.043	Neutral

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: rs1827603267; hg19: chr9-34990697;