1-65364610-G-GT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001256864.2(DNAJC6):c.194-22dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,441,052 control chromosomes in the GnomAD database, including 55 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00091 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0023 (52 hom.)
• Consequence: DNAJC6 NM_001256864.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.645

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 -10 ACMG points.

• BP6: Variant 1-65364610-G-GT is Benign according to our data. Variant chr1-65364610-G-GT is described in ClinVar as [Likely_benign]. Clinvar id is 1197078.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00226 (2970/1314184) while in subpopulation EAS AF= 0.0413 (1388/33600). AF 95% confidence interval is 0.0395. There are 52 homozygotes in gnomad4_exome. There are 1521 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC6	NM_001256864.2	c.194-22dup		intron_variant		ENST00000371069.5
DNAJC6	NM_001256865.2	c.-17-22dup		intron_variant
DNAJC6	NM_014787.4	c.23-22dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC6	ENST00000371069.5	c.194-22dup		intron_variant		1	NM_001256864.2	P4

Frequencies

GnomAD3 genomes AF: 0.000907 AC: 115 AN: 126848 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.000649

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00187

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.00172

Gnomad FIN AF: 0.00127

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000819

Gnomad OTH AF: 0.000564

GnomAD3 exomes AF: 0.0103 AC: 1019 AN: 99252 Hom.: 58 AF XY: 0.00994 AC XY: 520 AN XY: 52302

Gnomad AFR exome AF: 0.0111

Gnomad AMR exome AF: 0.0255

Gnomad ASJ exome AF: 0.00240

Gnomad EAS exome AF: 0.0430

Gnomad SAS exome AF: 0.00976

Gnomad FIN exome AF: 0.00417

Gnomad NFE exome AF: 0.00113

Gnomad OTH exome AF: 0.00647

GnomAD4 exome AF: 0.00226 AC: 2970 AN: 1314184 Hom.: 52 Cov.: 30 AF XY: 0.00233 AC XY: 1521 AN XY: 653042

Gnomad4 AFR exome AF: 0.00279

Gnomad4 AMR exome AF: 0.0156

Gnomad4 ASJ exome AF: 0.00201

Gnomad4 EAS exome AF: 0.0413

Gnomad4 SAS exome AF: 0.00607

Gnomad4 FIN exome AF: 0.00335

Gnomad4 NFE exome AF: 0.000250

Gnomad4 OTH exome AF: 0.00253

GnomAD4 genome AF: 0.000906 AC: 115 AN: 126868 Hom.: 3 Cov.: 31 AF XY: 0.00101 AC XY: 62 AN XY: 61216

Gnomad4 AFR AF: 0.000648

Gnomad4 AMR AF: 0.00187

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0113

Gnomad4 SAS AF: 0.00173

Gnomad4 FIN AF: 0.00127

Gnomad4 NFE AF: 0.0000819

Gnomad4 OTH AF: 0.000559

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs753560538; hg19: chr1-65830293;