chr1-65401708-C-G

Position:

• chr1-65401708-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000371069.5(DNAJC6):​c.2108-53C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 1,574,990 control chromosomes in the GnomAD database, including 288,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (34865 hom., cov: 31)
  • Exomes 𝑓: 0.59 (253794 hom.)
• Consequence: DNAJC6 ENST00000371069.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0920

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 1-65401708-C-G is Benign according to our data. Variant chr1-65401708-C-G is described in ClinVar as [Benign]. Clinvar id is 1280630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC6	NM_001256864.2	c.2108-53C>G		intron_variant		ENST00000371069.5	NP_001243793.1
DNAJC6	NM_014787.4	c.1937-53C>G		intron_variant			NP_055602.1
DNAJC6	NM_001256865.2	c.1898-53C>G		intron_variant			NP_001243794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC6	ENST00000371069.5	c.2108-53C>G		intron_variant		1	NM_001256864.2	ENSP00000360108.4
DNAJC6	ENST00000395325.7	c.1937-53C>G		intron_variant		1		ENSP00000378735.3
DNAJC6	ENST00000263441.11	c.1898-53C>G		intron_variant		2		ENSP00000263441.7

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101312 AN: 151912 Hom.: 34828 Cov.: 31

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.656

GnomAD4 exome AF: 0.593 AC: 843833 AN: 1422960 Hom.: 253794 AF XY: 0.596 AC XY: 420996 AN XY: 706492

Gnomad4 AFR exome AF: 0.864

Gnomad4 AMR exome AF: 0.627

Gnomad4 ASJ exome AF: 0.648

Gnomad4 EAS exome AF: 0.812

Gnomad4 SAS exome AF: 0.689

Gnomad4 FIN exome AF: 0.580

Gnomad4 NFE exome AF: 0.567

Gnomad4 OTH exome AF: 0.611

GnomAD4 genome AF: 0.667 AC: 101408 AN: 152030 Hom.: 34865 Cov.: 31 AF XY: 0.669 AC XY: 49670 AN XY: 74300

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.634

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.785

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.660

Alfa AF: 0.619 Hom.: 3749

Bravo AF: 0.678

Asia WGS AF: 0.742 AC: 2579 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4592284; hg19: chr1-65867391;