rs1330692

Positions:

• chr9-33034667-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001539.4(DNAJA1):​c.758+337T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,258 control chromosomes in the GnomAD database, including 1,316 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 0.12 (1316 hom., cov: 32)
• Consequence: DNAJA1 NM_001539.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102

Genes affected

DNAJA1 (HGNC:5229): (DnaJ heat shock protein family (Hsp40) member A1) This gene encodes a member of the DnaJ family of proteins, which act as heat shock protein 70 cochaperones. Heat shock proteins facilitate protein folding, trafficking, prevention of aggregation, and proteolytic degradation. Members of this family are characterized by a highly conserved N-terminal J domain, a glycine/phenylalanine-rich region, four CxxCxGxG zinc finger repeats, and a C-terminal substrate-binding domain. The J domain mediates the interaction with heat shock protein 70 to recruit substrates and regulate ATP hydrolysis activity. In humans, this gene has been implicated in positive regulation of virus replication through co-option by the influenza A virus. Several pseudogenes of this gene are found on other chromosomes. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJA1	NM_001539.4	c.758+337T>C		intron_variant		ENST00000330899.5	NP_001530.1
DNAJA1	NM_001314039.2	c.287+337T>C		intron_variant			NP_001300968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJA1	ENST00000330899.5	c.758+337T>C		intron_variant		1	NM_001539.4	ENSP00000369127	P1
DNAJA1	ENST00000465677.1	n.71+337T>C		intron_variant, non_coding_transcript_variant		2
DNAJA1	ENST00000495015.5	n.213+337T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18183 AN: 152140 Hom.: 1324 Cov.: 32

Gnomad AFR AF: 0.0356

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.153

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.119 AC: 18169 AN: 152258 Hom.: 1316 Cov.: 32 AF XY: 0.120 AC XY: 8970 AN XY: 74446

Gnomad4 AFR AF: 0.0354

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.154

Alfa AF: 0.146 Hom.: 2237

Bravo AF: 0.118

Asia WGS AF: 0.233 AC: 810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.80

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

Other links and lift over

dbSNP: rs1330692; hg19: chr9-33034665;