chr10-72336621-TTC-CTG

Variant names:

• chr10-72336621-TTC-CTG
• NM_017626.7:c.907_909delGAAinsCAG
• DNAJB12 p.Glu303Gln

Variant summary

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

The NM_017626.7(DNAJB12):​c.907_909delGAAinsCAG​(p.Glu303Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E303K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DNAJB12 NM_017626.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.23
• Publications: 0 publications found

Genes affected

DNAJB12 (HGNC:14891): (DnaJ heat shock protein family (Hsp40) member B12) DNAJB12 belongs to the evolutionarily conserved DNAJ/HSP40 family of proteins, which regulate molecular chaperone activity by stimulating ATPase activity. DNAJ proteins may have up to 3 distinct domains: a conserved 70-amino acid J domain, usually at the N terminus; a glycine/phenylalanine (G/F)-rich region; and a cysteine-rich domain containing 4 motifs resembling a zinc finger domain (Ohtsuka and Hata, 2000 [PubMed 11147971]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017626.7. 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
	DNAJB12	NM_017626.7	MANE Select	c.907_909delGAAinsCAG	p.Glu303Gln	missense	N/A	NP_060096.4
	DNAJB12	NM_001365080.3		c.907_909delGAAinsCAG	p.Glu303Gln	missense	N/A	NP_001352009.1	Q9NXW2-2
	DNAJB12	NM_001002762.5		c.907_909delGAAinsCAG	p.Glu303Gln	missense	N/A	NP_001002762.3	Q9NXW2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB12	ENST00000444643.8	TSL:1 MANE Select	c.907_909delGAAinsCAG	p.Glu303Gln	missense	N/A	ENSP00000403313.2	Q9NXW2-1
	DNAJB12	ENST00000394903.6	TSL:1	c.1009_1011delGAAinsCAG	p.Glu337Gln	missense	N/A	ENSP00000378363.2	J3KPS0
	DNAJB12	ENST00000473051.1	TSL:1	n.243_245delGAAinsCAG		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2

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: chr10-74096379;