chr20-63915744-A-G

Position:

• chr20-63915744-A-G

Variant summary

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

The NM_025219.3(DNAJC5):​c.-11-12591A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,108 control chromosomes in the GnomAD database, including 19,603 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 0.47 (19603 hom., cov: 33)
• Consequence: DNAJC5 NM_025219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

Genes affected

DNAJC5 (HGNC:16235): (DnaJ heat shock protein family (Hsp40) member C5) This gene is a member of the J protein family. J proteins function in many cellular processes by regulating the ATPase activity of 70 kDa heat shock proteins. The encoded protein plays a role in membrane trafficking and protein folding, and has been shown to have anti-neurodegenerative properties. The encoded protein is known to play a role in cystic fibrosis and Huntington's disease. A pseudogene of this gene is located on the short arm of chromosome 8. [provided by RefSeq, Nov 2010]

ENSG00000290226 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC5	NM_025219.3	c.-11-12591A>G		intron_variant		ENST00000360864.9	NP_079495.1
DNAJC5	XM_047440509.1	c.-11-12591A>G		intron_variant			XP_047296465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC5	ENST00000360864.9	c.-11-12591A>G		intron_variant		1	NM_025219.3	ENSP00000354111.4
DNAJC5	ENST00000470551.1	n.-11-12591A>G		intron_variant		2		ENSP00000434744.1
ENSG00000290226	ENST00000703636.1	n.454-12591A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70747 AN: 151990 Hom.: 19541 Cov.: 33

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.466 AC: 70874 AN: 152108 Hom.: 19603 Cov.: 33 AF XY: 0.471 AC XY: 35061 AN XY: 74368

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.942

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.433

Alfa AF: 0.433 Hom.: 2369

Bravo AF: 0.490

Asia WGS AF: 0.650 AC: 2258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs2427547; hg19: chr20-62547097;