rs6011225

Positions:

• chr20-63917198-A-C
• chr20-63917198-A-G
• chr20-63917198-A-T

Variant summary

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

The NM_025219.3(DNAJC5):​c.-11-11137A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 152,066 control chromosomes in the GnomAD database, including 16,398 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 0.43 (16398 hom., cov: 33)
• Consequence: DNAJC5 NM_025219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• 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	UniProt
DNAJC5	NM_025219.3	c.-11-11137A>C		intron_variant		ENST00000360864.9
DNAJC5	XM_047440509.1	c.-11-11137A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC5	ENST00000360864.9	c.-11-11137A>C		intron_variant		1	NM_025219.3	P1
DNAJC5	ENST00000470551.1	c.-11-11137A>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65860 AN: 151948 Hom.: 16346 Cov.: 33

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.434 AC: 65974 AN: 152066 Hom.: 16398 Cov.: 33 AF XY: 0.441 AC XY: 32752 AN XY: 74336

Gnomad4 AFR AF: 0.602

Gnomad4 AMR AF: 0.488

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: 0.415

Alfa AF: 0.238 Hom.: 559

Bravo AF: 0.454

Asia WGS AF: 0.642 AC: 2229 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	1.8
DANN	Benign	0.37

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: rs6011225; hg19: chr20-62548551;