rs11645060

Positions:

• chr16-4441060-G-A

Variant summary

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

The NM_005147.6(DNAJA3):​c.430-315G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0495 in 439,494 control chromosomes in the GnomAD database, including 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 0.043 (198 hom., cov: 31)
  • Exomes 𝑓: 0.053 (494 hom.)
• Consequence: DNAJA3 NM_005147.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600

Genes affected

DNAJA3 (HGNC:11808): (DnaJ heat shock protein family (Hsp40) member A3) This gene encodes a member of the DNAJ/Hsp40 protein family. DNAJ/Hsp40 proteins stimulate the ATPase activity of Hsp70 chaperones and play critical roles in protein folding, degradation, and multimeric complex assembly. The encoded protein is localized to mitochondria and mediates several cellular processes including proliferation, survival and apoptotic signal transduction. The encoded protein also plays a critical role in tumor suppression through interactions with oncogenic proteins including ErbB2 and the p53 tumor suppressor protein. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]

DNAJA3 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.0621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJA3	NM_005147.6	c.430-315G>A		intron_variant		ENST00000262375.11	NP_005138.3
DNAJA3	NM_001135110.3	c.430-315G>A		intron_variant			NP_001128582.1
DNAJA3	NM_001286516.2	c.102-446G>A		intron_variant			NP_001273445.1
DNAJA3	XM_047434875.1	c.430-315G>A		intron_variant			XP_047290831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJA3	ENST00000262375.11	c.430-315G>A		intron_variant		1	NM_005147.6	ENSP00000262375.4

Frequencies

GnomAD3 genomes AF: 0.0426 AC: 6481 AN: 152218 Hom.: 198 Cov.: 31

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0399

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0410

Gnomad FIN AF: 0.0383

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0636

Gnomad OTH AF: 0.0569

GnomAD4 exome AF: 0.0533 AC: 15292 AN: 287158 Hom.: 494 Cov.: 0 AF XY: 0.0539 AC XY: 7982 AN XY: 148106

Gnomad4 AFR exome AF: 0.0110

Gnomad4 AMR exome AF: 0.0415

Gnomad4 ASJ exome AF: 0.0896

Gnomad4 EAS exome AF: 0.000194

Gnomad4 SAS exome AF: 0.0464

Gnomad4 FIN exome AF: 0.0395

Gnomad4 NFE exome AF: 0.0622

Gnomad4 OTH exome AF: 0.0561

GnomAD4 genome AF: 0.0425 AC: 6479 AN: 152336 Hom.: 198 Cov.: 31 AF XY: 0.0425 AC XY: 3164 AN XY: 74496

Gnomad4 AFR AF: 0.0106

Gnomad4 AMR AF: 0.0398

Gnomad4 ASJ AF: 0.0867

Gnomad4 EAS AF: 0.000770

Gnomad4 SAS AF: 0.0408

Gnomad4 FIN AF: 0.0383

Gnomad4 NFE AF: 0.0637

Gnomad4 OTH AF: 0.0568

Alfa AF: 0.0629 Hom.: 442

Bravo AF: 0.0419

Asia WGS AF: 0.0160 AC: 55 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	3.3
DANN	Benign	0.85

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: rs11645060; hg19: chr16-4491061;