Genetic Variant DNAJA4:c.-14C>T (chr15-78264750-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001130182.2(DNAJA4):c.-14C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0053 in 1,571,470 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0053 ( 43 hom. )

Consequence

DNAJA4
NM_001130182.2 5_prime_UTR

Scores

Splicing: ADA: 0.00001808

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.49

Publications

1 publications found

Variant links:

Genes affected

DNAJA4 (HGNC:14885): (DnaJ heat shock protein family (Hsp40) member A4) Enables chaperone binding activity and unfolded protein binding activity. Involved in several processes, including negative regulation of endothelial cell migration; negative regulation of inclusion body assembly; and protein refolding. Located in cytosol and membrane. [provided by Alliance of Genome Resources, Apr 2022]

DNAJA4 links:

DNAJA4-DT (HGNC:55412): (DNAJA4 divergent transcript)

DNAJA4-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 15-78264750-C-T is Benign according to our data. Variant chr15-78264750-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2645609.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJA4	NM_001130182.2 link	c.-14C>T		5_prime_UTR_variant	Exon 1 of 7	ENST00000394852.8	NP_001123654.1	Q8WW22-1Q69YX3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJA4	ENST00000394852.8 link	c.-14C>T		5_prime_UTR_variant	Exon 1 of 7	1	NM_001130182.2	ENSP00000378321.3		Q8WW22-1

Frequencies

GnomAD3 genomes

AF:

0.00489

AC:

739

AN:

151268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000774

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00302

Gnomad ASJ

AF:

0.00174

Gnomad EAS

AF:

0.000388

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0119

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00772

Gnomad OTH

AF:

0.00337

GnomAD2 exomes

AF:

0.00443

AC:

955

AN:

215694

AF XY:

0.00443

show subpopulations

Gnomad AFR exome

AF:

0.00147

Gnomad AMR exome

AF:

0.00143

Gnomad ASJ exome

AF:

0.00142

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0111

Gnomad NFE exome

AF:

0.00637

Gnomad OTH exome

AF:

0.00562

GnomAD4 exome

AF:

0.00535

AC:

7597

AN:

1420090

Hom.:

Cov.:

AF XY:

0.00526

AC XY:

3711

AN XY:

705500

show subpopulations

African (AFR)

AF:

0.000808

AC:

AN:

30924

American (AMR)

AF:

0.00152

AC:

AN:

42182

Ashkenazi Jewish (ASJ)

AF:

0.00145

AC:

AN:

24758

East Asian (EAS)

AF:

0.00

AC:

AN:

36320

South Asian (SAS)

AF:

0.00120

AC:

101

AN:

83906

European-Finnish (FIN)

AF:

0.0112

AC:

558

AN:

49808

Middle Eastern (MID)

AF:

0.000535

AC:

AN:

5604

European-Non Finnish (NFE)

AF:

0.00604

AC:

6573

AN:

1088604

Other (OTH)

AF:

0.00409

AC:

237

AN:

57984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

381

763

1144

1526

1907

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

208

416

624

832

1040

<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:

0.00488

AC:

739

AN:

151380

Hom.:

Cov.:

AF XY:

0.00485

AC XY:

359

AN XY:

73980

show subpopulations

African (AFR)

AF:

0.000772

AC:

AN:

41460

American (AMR)

AF:

0.00302

AC:

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.00174

AC:

AN:

3454

East Asian (EAS)

AF:

0.000389

AC:

AN:

5142

South Asian (SAS)

AF:

0.000208

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.0119

AC:

122

AN:

10228

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00772

AC:

523

AN:

67748

Other (OTH)

AF:

0.00334

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

111

148

185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00590

Hom.:

Bravo

AF:

0.00412

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

DNAJA4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

2.5

PromoterAI

0.029

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000018

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over