1-65265179-A-G

Variant summary

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

The ENST00000395325.7(DNAJC6):c.22+247A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 152,076 control chromosomes in the GnomAD database, including 34,266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.66 (34266 hom., cov: 33)
• Consequence: DNAJC6 ENST00000395325.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00900

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=-0.69).
• BP6: Variant 1-65265179-A-G is Benign according to our data. Variant chr1-65265179-A-G is described in ClinVar as [Benign]. Clinvar id is 1181884.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC6	NM_001256865.2	c.-131+247A>G		intron_variant
DNAJC6	NM_014787.4	c.22+247A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC6	ENST00000395325.7	c.22+247A>G		intron_variant		1		A1
DNAJC6	ENST00000263441.11	c.-131+247A>G		intron_variant		2		A1
DNAJC6	ENST00000494710.6	c.115+10530A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100072 AN: 151958 Hom.: 34262 Cov.: 33

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.873

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.658 AC: 100112 AN: 152076 Hom.: 34266 Cov.: 33 AF XY: 0.658 AC XY: 48872 AN XY: 74320

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.666

Gnomad4 ASJ AF: 0.798

Gnomad4 EAS AF: 0.771

Gnomad4 SAS AF: 0.873

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.752

Gnomad4 OTH AF: 0.678

Alfa AF: 0.726 Hom.: 22458

Bravo AF: 0.649

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	-0.69
Cadd	Benign	12
Dann	Benign	0.86

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: rs1749971; hg19: chr1-65730862;