10-72335295-G-A

Position:

• chr10-72335295-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017626.7(DNAJB12):​c.*30+485C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0471 in 987,580 control chromosomes in the GnomAD database, including 3,564 homozygotes. 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: 𝑓 0.12 (2347 hom., cov: 33)
  • Exomes 𝑓: 0.034 (1217 hom.)
• Consequence: DNAJB12 NM_017626.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJB12	NM_017626.7	c.*30+485C>T		intron_variant		ENST00000444643.8	NP_060096.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJB12	ENST00000444643.8	c.*30+485C>T		intron_variant		1	NM_017626.7	ENSP00000403313	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17704 AN: 152128 Hom.: 2325 Cov.: 33

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0593

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0683

Gnomad FIN AF: 0.0213

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0282

Gnomad OTH AF: 0.0961

GnomAD4 exome AF: 0.0344 AC: 28769 AN: 835334 Hom.: 1217 Cov.: 32 AF XY: 0.0337 AC XY: 13020 AN XY: 385992

Gnomad4 AFR exome AF: 0.329

Gnomad4 AMR exome AF: 0.0492

Gnomad4 ASJ exome AF: 0.0231

Gnomad4 EAS exome AF: 0.130

Gnomad4 SAS exome AF: 0.0608

Gnomad4 FIN exome AF: 0.0206

Gnomad4 NFE exome AF: 0.0267

Gnomad4 OTH exome AF: 0.0526

GnomAD4 genome AF: 0.117 AC: 17768 AN: 152246 Hom.: 2347 Cov.: 33 AF XY: 0.114 AC XY: 8508 AN XY: 74444

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.0592

Gnomad4 ASJ AF: 0.0271

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.0677

Gnomad4 FIN AF: 0.0213

Gnomad4 NFE AF: 0.0282

Gnomad4 OTH AF: 0.0956

Alfa AF: 0.0782 Hom.: 175

Bravo AF: 0.130

Asia WGS AF: 0.121 AC: 419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.60
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7894262; hg19: chr10-74095053;