rs1570868

Positions:

• chr1-65364925-T-C

Variant summary

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

The NM_001256864.2(DNAJC6):​c.344+140T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 1,207,840 control chromosomes in the GnomAD database, including 188,230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.53 (21711 hom., cov: 31)
  • Exomes 𝑓: 0.56 (166519 hom.)
• Consequence: DNAJC6 NM_001256864.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.72

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=-0.89).
• BP6: Variant 1-65364925-T-C is Benign according to our data. Variant chr1-65364925-T-C is described in ClinVar as [Benign]. Clinvar id is 1222461.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC6	NM_001256864.2	c.344+140T>C		intron_variant		ENST00000371069.5
DNAJC6	NM_001256865.2	c.134+140T>C		intron_variant
DNAJC6	NM_014787.4	c.173+140T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC6	ENST00000371069.5	c.344+140T>C		intron_variant		1	NM_001256864.2	P4

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80570 AN: 151796 Hom.: 21709 Cov.: 31

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.564

GnomAD4 exome AF: 0.556 AC: 587056 AN: 1055926 Hom.: 166519 AF XY: 0.559 AC XY: 296221 AN XY: 529750

Gnomad4 AFR exome AF: 0.477

Gnomad4 AMR exome AF: 0.475

Gnomad4 ASJ exome AF: 0.578

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.598

Gnomad4 FIN exome AF: 0.471

Gnomad4 NFE exome AF: 0.574

Gnomad4 OTH exome AF: 0.550

GnomAD4 genome AF: 0.531 AC: 80613 AN: 151914 Hom.: 21711 Cov.: 31 AF XY: 0.525 AC XY: 38942 AN XY: 74198

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.560

Alfa AF: 0.575 Hom.: 33854

Bravo AF: 0.529

Asia WGS AF: 0.431 AC: 1497 AN: 3476

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	-0.89
CADD	Benign	0.049
DANN	Benign	0.54

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: rs1570868; hg19: chr1-65830608; COSMIC: COSV54771795; COSMIC: COSV54771795;