chr9-34990673-CCC-GCT

Variant names:

• chr9-34990673-CCC-GCT
• NM_001349723.3:c.43_45delCCCinsGCT
• DNAJB5 p.Pro15Ala

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM5

The NM_001349723.3(DNAJB5):​c.43_45delCCCinsGCT​(p.Pro15Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P15S) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAJB5 NM_001349723.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.87
• 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 2 ACMG points.

• PM5: Other missense variant is known to change same aminoacid residue: Variant chr9-34990673-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 243086.

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.43_45delCCCinsGCT	p.Pro15Ala	missense	N/A	NP_001336652.1	O75953-4
	DNAJB5	NM_001135005.3		c.43_45delCCCinsGCT	p.Pro15Ala	missense	N/A	NP_001128477.1	O75953-4
	DNAJB5	NM_001349725.2		c.-72_-70delCCCinsGCT		splice_region	Exon 2 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.43_45delCCCinsGCT	p.Pro15Ala	missense	N/A	ENSP00000507741.1	O75953-4
	DNAJB5	ENST00000454002.6	TSL:1	c.43_45delCCCinsGCT	p.Pro15Ala	missense	N/A	ENSP00000413684.2	O75953-4
	DNAJB5	ENST00000312316.9	TSL:1	c.-35+842_-35+844delCCCinsGCT		intron	N/A	ENSP00000312517.5	O75953-3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-34990670;