rs6011226

Positions:

• chr20-63918428-T-A

Variant summary

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

The XM_047440634.1(LOC124904951):​c.-972T>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 152,014 control chromosomes in the GnomAD database, including 10,746 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 (10746 hom., cov: 33)
• Consequence: LOC124904951 XM_047440634.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.913

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124904951	XM_047440634.1	c.-972T>A		5_prime_UTR_variant	1/1		XP_047296590.1
DNAJC5	NM_025219.3	c.-11-9907T>A		intron_variant		ENST00000360864.9	NP_079495.1
DNAJC5	XM_047440509.1	c.-11-9907T>A		intron_variant			XP_047296465.1
DNAJC5	XM_047440511.1	c.-12+710T>A		intron_variant			XP_047296467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC5	ENST00000360864.9	c.-11-9907T>A		intron_variant		1	NM_025219.3	ENSP00000354111	P1
DNAJC5	ENST00000470551.1	c.-11-9907T>A		intron_variant, NMD_transcript_variant		2		ENSP00000434744

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52234 AN: 151896 Hom.: 10709 Cov.: 33

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.330

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: 52326 AN: 152014 Hom.: 10746 Cov.: 33 AF XY: 0.353 AC XY: 26189 AN XY: 74294

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.811

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.324

Alfa AF: 0.292 Hom.: 940

Bravo AF: 0.362

Asia WGS AF: 0.553 AC: 1920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.42
DANN	Benign	0.79

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: rs6011226; hg19: chr20-62549781;