rs2304634

Variant names:

• chr16-4450543-C-A
• rs2304634
• NM_005147.6:c.1339+46C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-4450543-C-A
• chr16-4450543-C-G
• chr16-4450543-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005147.6(DNAJA3):​c.1339+46C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAJA3 NM_005147.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJA3	NM_005147.6	c.1339+46C>A		intron_variant	Intron 10 of 11	ENST00000262375.11	NP_005138.3
DNAJA3	NM_001135110.3	c.1339+46C>A		intron_variant	Intron 10 of 10		NP_001128582.1
DNAJA3	NM_001286516.2	c.880+46C>A		intron_variant	Intron 8 of 8		NP_001273445.1
DNAJA3	XM_047434875.1	c.1339+46C>A		intron_variant	Intron 10 of 10		XP_047290831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJA3	ENST00000262375.11	c.1339+46C>A		intron_variant	Intron 10 of 11	1	NM_005147.6	ENSP00000262375.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1300168 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 644956

African (AFR) AF: 0.00 AC: 0 AN: 29996

American (AMR) AF: 0.00 AC: 0 AN: 34906

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24056

East Asian (EAS) AF: 0.00 AC: 0 AN: 35806

South Asian (SAS) AF: 0.00 AC: 0 AN: 75822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5462

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 989940

Other (OTH) AF: 0.00 AC: 0 AN: 54584

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.17
DANN	Benign	0.82
PhyloP100		-1.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2304634; hg19: chr16-4500544;