rs2375699

chr1-65342598-G-Achr1-65342598-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001256864.2(DNAJC6):c.194-22037G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,954 control chromosomes in the GnomAD database, including 20,324 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (20324 hom., cov: 32)
• Consequence: DNAJC6 NM_001256864.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC6	NM_001256864.2	c.194-22037G>A		intron_variant		ENST00000371069.5
DNAJC6	NM_001256865.2	c.-130-3013G>A		intron_variant
DNAJC6	NM_014787.4	c.23-22037G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC6	ENST00000371069.5	c.194-22037G>A		intron_variant		1	NM_001256864.2	P4

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77811 AN: 151838 Hom.: 20320 Cov.: 32

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.512 AC: 77843 AN: 151954 Hom.: 20324 Cov.: 32 AF XY: 0.500 AC XY: 37099 AN XY: 74258

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.537

Alfa AF: 0.538 Hom.: 45115

Bravo AF: 0.522

Asia WGS AF: 0.352 AC: 1227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.50
Dann	Benign	0.64

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: rs2375699; hg19: chr1-65808281;