rs17127601

chr1-65408189-A-G

Variant summary

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

The NM_001256864.2(DNAJC6):c.2492-452A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,180 control chromosomes in the GnomAD database, including 3,084 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 0.18 (3084 hom., cov: 32)
• Consequence: DNAJC6 NM_001256864.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.926

Genes affected

DNAJC6 (HGNC:15469): (DnaJ heat shock protein family (Hsp40) member C6) DNAJC6 belongs to the evolutionarily conserved DNAJ/HSP40 family of proteins, which regulate molecular chaperone activity by stimulating ATPase activity. DNAJ proteins may have up to 3 distinct domains: a conserved 70-amino acid J domain, usually at the N terminus, a glycine/phenylalanine (G/F)-rich region, and a cysteine-rich domain containing 4 motifs resembling a zinc finger domain (Ohtsuka and Hata, 2000 [PubMed 11147971]).[supplied by OMIM, Mar 2008]

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 (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC6	NM_001256864.2	c.2492-452A>G		intron_variant		ENST00000371069.5
DNAJC6	NM_001256865.2	c.2282-452A>G		intron_variant
DNAJC6	NM_014787.4	c.2321-452A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC6	ENST00000371069.5	c.2492-452A>G		intron_variant		1	NM_001256864.2	P4
DNAJC6	ENST00000395325.7	c.2321-452A>G		intron_variant		1		A1
DNAJC6	ENST00000263441.11	c.2282-452A>G		intron_variant		2		A1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27986 AN: 152062 Hom.: 3067 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.0734

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.184 AC: 28036 AN: 152180 Hom.: 3084 Cov.: 32 AF XY: 0.184 AC XY: 13677 AN XY: 74412

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.0726

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.190

Alfa AF: 0.141 Hom.: 2358

Bravo AF: 0.204

Asia WGS AF: 0.128 AC: 445 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	5.1
Dann	Benign	0.45

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: rs17127601; hg19: chr1-65873872;