1-65264541-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000494710.6(DNAJC6):c.115+9892G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,826 control chromosomes in the GnomAD database, including 15,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.45 (15431 hom., cov: 31)
• Consequence: DNAJC6 ENST00000494710.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.655

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-65264541-G-C is Benign according to our data. Variant chr1-65264541-G-C is described in ClinVar as [Benign]. Clinvar id is 1282584.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC6	ENST00000494710.6	c.115+9892G>C		intron_variant		5
DNAJC6	ENST00000463018.5	n.85+16238G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68240 AN: 151708 Hom.: 15425 Cov.: 31

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.450 AC: 68283 AN: 151826 Hom.: 15431 Cov.: 31 AF XY: 0.450 AC XY: 33400 AN XY: 74168

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.471

Alfa AF: 0.445 Hom.: 1940

Bravo AF: 0.450

Asia WGS AF: 0.502 AC: 1745 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.8
Dann	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3828040; hg19: chr1-65730224; COSMIC: COSV54780849;