1-65413569-A-G

Position:

• chr1-65413569-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.*544A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,946 control chromosomes in the GnomAD database, including 18,498 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 0.49 (18488 hom., cov: 31)
  • Exomes 𝑓: 0.46 (10 hom.)
• Consequence: DNAJC6 NM_001256864.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC6	NM_001256864.2	c.*544A>G		3_prime_UTR_variant	19/19	ENST00000371069.5
DNAJC6	NM_001256865.2	c.*544A>G		3_prime_UTR_variant	20/20
DNAJC6	NM_014787.4	c.*544A>G		3_prime_UTR_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC6	ENST00000371069.5	c.*544A>G		3_prime_UTR_variant	19/19	1	NM_001256864.2	P4
DNAJC6	ENST00000395325.7	c.*544A>G		3_prime_UTR_variant	19/19	1		A1
DNAJC6	ENST00000263441.11	c.*544A>G		3_prime_UTR_variant	20/20	2		A1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73873 AN: 151716 Hom.: 18460 Cov.: 31

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.487

GnomAD4 exome AF: 0.465 AC: 53 AN: 114 Hom.: 10 Cov.: 0 AF XY: 0.481 AC XY: 26 AN XY: 54

Gnomad4 AMR exome AF: 0.667

Gnomad4 EAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.453

GnomAD4 genome AF: 0.487 AC: 73949 AN: 151832 Hom.: 18488 Cov.: 31 AF XY: 0.491 AC XY: 36446 AN XY: 74198

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.859

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.487

Alfa AF: 0.458 Hom.: 21704

Bravo AF: 0.486

Asia WGS AF: 0.645 AC: 2245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.68
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs10493377; hg19: chr1-65879252;