chr16-4450543-C-T

Position:

• chr16-4450543-C-T

Variant summary

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

The NM_005147.6(DNAJA3):​c.1339+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 1,449,482 control chromosomes in the GnomAD database, including 317,121 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 0.58 (27085 hom., cov: 32)
  • Exomes 𝑓: 0.66 (290036 hom.)
• Consequence: DNAJA3 NM_005147.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJA3	NM_005147.6	c.1339+46C>T		intron_variant		ENST00000262375.11
DNAJA3	NM_001135110.3	c.1339+46C>T		intron_variant
DNAJA3	NM_001286516.2	c.880+46C>T		intron_variant
DNAJA3	XM_047434875.1	c.1339+46C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJA3	ENST00000262375.11	c.1339+46C>T		intron_variant		1	NM_005147.6	P3

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87756 AN: 151908 Hom.: 27069 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.596

GnomAD3 exomes AF: 0.629 AC: 104242 AN: 165720 Hom.: 33435 AF XY: 0.633 AC XY: 56087 AN XY: 88654

Gnomad AFR exome AF: 0.362

Gnomad AMR exome AF: 0.591

Gnomad ASJ exome AF: 0.603

Gnomad EAS exome AF: 0.620

Gnomad SAS exome AF: 0.530

Gnomad FIN exome AF: 0.736

Gnomad NFE exome AF: 0.692

Gnomad OTH exome AF: 0.636

GnomAD4 exome AF: 0.665 AC: 862515 AN: 1297456 Hom.: 290036 Cov.: 17 AF XY: 0.662 AC XY: 426291 AN XY: 643710

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.575

Gnomad4 ASJ exome AF: 0.603

Gnomad4 EAS exome AF: 0.651

Gnomad4 SAS exome AF: 0.538

Gnomad4 FIN exome AF: 0.722

Gnomad4 NFE exome AF: 0.689

Gnomad4 OTH exome AF: 0.629

GnomAD4 genome AF: 0.578 AC: 87812 AN: 152026 Hom.: 27085 Cov.: 32 AF XY: 0.576 AC XY: 42822 AN XY: 74286

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.632

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.726

Gnomad4 NFE AF: 0.691

Gnomad4 OTH AF: 0.590

Alfa AF: 0.583 Hom.: 4428

Bravo AF: 0.557

Asia WGS AF: 0.488 AC: 1700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.14
DANN	Benign	0.81

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: rs2304634; hg19: chr16-4500544; COSMIC: COSV52163025; COSMIC: COSV52163025;