dbSNP rs11645060: DNAJA3:c.430-315G>A (chr16-4441060-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00600

Publications

1 publications found

Variant links:

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

DNAJA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
DNAJA3	NM_005147.6 link	c.430-315G>A	intron_variant	Intron 3 of 11	ENST00000262375.11	NP_005138.3	Q96EY1-1Q53G26Q59E88
DNAJA3	NM_001135110.3 link	c.430-315G>A	intron_variant	Intron 3 of 10		NP_001128582.1	Q96EY1-2B3KM81
DNAJA3	NM_001286516.2 link	c.102-446G>A	intron_variant	Intron 1 of 8		NP_001273445.1	Q96EY1-3B3KM81
DNAJA3	XM_047434875.1 link	c.430-315G>A	intron_variant	Intron 3 of 10		XP_047290831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJA3	ENST00000262375.11 link	c.430-315G>A		intron_variant	Intron 3 of 11	1	NM_005147.6	ENSP00000262375.4		Q96EY1-1

Frequencies

GnomAD3 genomes

AF:

0.0426

AC:

6481

AN:

152218

Hom.:

198

Cov.:

show subpopulations

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.:

AF XY:

0.0539

AC XY:

7982

AN XY:

148106

show subpopulations

African (AFR)

AF:

0.0110

AC:

105

AN:

9586

American (AMR)

AF:

0.0415

AC:

381

AN:

9184

Ashkenazi Jewish (ASJ)

AF:

0.0896

AC:

861

AN:

9608

East Asian (EAS)

AF:

0.000194

AC:

AN:

20648

South Asian (SAS)

AF:

0.0464

AC:

1033

AN:

22254

European-Finnish (FIN)

AF:

0.0395

AC:

734

AN:

18602

Middle Eastern (MID)

AF:

0.0701

AC:

AN:

1384

European-Non Finnish (NFE)

AF:

0.0622

AC:

11083

AN:

178158

Other (OTH)

AF:

0.0561

AC:

994

AN:

17734

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

661

1323

1984

2646

3307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0425

AC:

6479

AN:

152336

Hom.:

198

Cov.:

AF XY:

0.0425

AC XY:

3164

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0106

AC:

440

AN:

41590

American (AMR)

AF:

0.0398

AC:

609

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0867

AC:

301

AN:

3470

East Asian (EAS)

AF:

0.000770

AC:

AN:

5192

South Asian (SAS)

AF:

0.0408

AC:

197

AN:

4828

European-Finnish (FIN)

AF:

0.0383

AC:

406

AN:

10612

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0637

AC:

4330

AN:

68028

Other (OTH)

AF:

0.0568

AC:

120

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

330

660

989

1319

1649

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0597

Hom.:

551

Bravo

AF:

0.0419

Asia WGS

AF:

0.0160

AC:

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

(source)

DANN

Benign

0.85

PhyloP100

-0.0060

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over