15-78264750-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000394855.7(DNAJA4):c.81-7C>T variant causes a splice region, splice polypyrimidine tract, 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 ENST00000394855.7 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001808
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.49

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]

ACMG classification

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 GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJA4	NM_001130182.2	c.-14C>T		5_prime_UTR_variant	1/7	ENST00000394852.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJA4	ENST00000394852.8	c.-14C>T		5_prime_UTR_variant	1/7	1	NM_001130182.2	P1

Frequencies

GnomAD3 genomes AF: 0.00489 AC: 739 AN: 151268 Hom.: 5 Cov.: 33

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.: 9 AF XY: 0.00443 AC XY: 525 AN XY: 118644

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.: 43 Cov.: 33 AF XY: 0.00526 AC XY: 3711 AN XY: 705500

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.: 5 Cov.: 33 AF XY: 0.00485 AC XY: 359 AN XY: 73980

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.: 5

Bravo AF: 0.00412

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	16
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

Other links and lift over

dbSNP: rs578060742; hg19: chr15-78557092;