Variant 15-78264750-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_018602.4(DNAJA4):c.81-7C>T variant causes a splice region, intron 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. 3/3 splice prediction tools predict no significant impact on normal splicing. 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_018602.4 splice_region, intron

Scores

Splicing: ADA: 0.00001808

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.49

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 (HGNC:):

DNAJA4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
DNAJA4	NM_001130182.2 linkuse as main transcript	c.-14C>T		5_prime_UTR_variant	1/7	ENST00000394852.8	NP_001123654.1	Q8WW22-1Q69YX3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJA4	ENST00000394852.8 linkuse as main transcript	c.-14C>T		5_prime_UTR_variant	1/7	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

GnomAD3 exomes

AF:

0.00443

AC:

955

AN:

215694

Hom.:

AF XY:

0.00443

AC XY:

525

AN XY:

118644

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 SAS exome

AF:

0.00117

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

Gnomad4 AFR exome

AF:

0.000808

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.00145

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00120

Gnomad4 FIN exome

AF:

0.0112

Gnomad4 NFE exome

AF:

0.00604

Gnomad4 OTH exome

AF:

0.00409

GnomAD4 genome

AF:

0.00488

AC:

739

AN:

151380

Hom.:

Cov.:

AF XY:

0.00485

AC XY:

359

AN XY:

73980

show subpopulations

Gnomad4 AFR

AF:

0.000772

Gnomad4 AMR

AF:

0.00302

Gnomad4 ASJ

AF:

0.00174

Gnomad4 EAS

AF:

0.000389

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0119

Gnomad4 NFE

AF:

0.00772

Gnomad4 OTH

AF:

0.00334

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

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

DNAJA4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.92

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over