rs2427554

Positions:

• chr20-63918212-G-A

Variant summary

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

The XM_047440634.1(LOC124904951):​c.-1188G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,892 control chromosomes in the GnomAD database, including 10,692 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 0.34 (10692 hom., cov: 32)
• Consequence: LOC124904951 XM_047440634.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167

Genes affected

LOC124904951 (HGNC:):

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124904951	XM_047440634.1	c.-1188G>A		5_prime_UTR_variant	1/1
DNAJC5	NM_025219.3	c.-11-10123G>A		intron_variant		ENST00000360864.9
DNAJC5	XM_047440509.1	c.-11-10123G>A		intron_variant
DNAJC5	XM_047440511.1	c.-12+494G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC5	ENST00000360864.9	c.-11-10123G>A		intron_variant		1	NM_025219.3	P1
DNAJC5	ENST00000470551.1	c.-11-10123G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52095 AN: 151774 Hom.: 10655 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.344 AC: 52187 AN: 151892 Hom.: 10692 Cov.: 32 AF XY: 0.352 AC XY: 26114 AN XY: 74220

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.810

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.325

Alfa AF: 0.247 Hom.: 9365

Bravo AF: 0.361

Asia WGS AF: 0.553 AC: 1921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2427554; hg19: chr20-62549565;