Variant 16-4450543-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.48

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 links:

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ACMG classification

Classification made for transcript

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	Effect	MANE
DNAJA3	NM_005147.6 linkuse as main transcript	c.1339+46C>T	intron_variant	ENST00000262375.11
DNAJA3	NM_001135110.3 linkuse as main transcript	c.1339+46C>T	intron_variant
DNAJA3	NM_001286516.2 linkuse as main transcript	c.880+46C>T	intron_variant
DNAJA3	XM_047434875.1 linkuse as main transcript	c.1339+46C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJA3	ENST00000262375.11 linkuse as main transcript	c.1339+46C>T		intron_variant		1	NM_005147.6	P3	Q96EY1-1

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87756

AN:

151908

Hom.:

27069

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.662

AC XY:

426291

AN XY:

643710

show subpopulations

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.:

AF XY:

0.576

AC XY:

42822

AN XY:

74286

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over