1-65341729-T-C

Position:

• chr1-65341729-T-C

Variant summary

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

The NM_001256864.2(DNAJC6):​c.194-22906T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 151,778 control chromosomes in the GnomAD database, including 31,343 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 0.63 (31343 hom., cov: 29)
• Consequence: DNAJC6 NM_001256864.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJC6	NM_001256864.2	c.194-22906T>C		intron_variant		ENST00000371069.5
DNAJC6	NM_001256865.2	c.-130-3882T>C		intron_variant
DNAJC6	NM_014787.4	c.23-22906T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJC6	ENST00000371069.5	c.194-22906T>C		intron_variant		1	NM_001256864.2	P4

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95086 AN: 151660 Hom.: 31298 Cov.: 29

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.627 AC: 95175 AN: 151778 Hom.: 31343 Cov.: 29 AF XY: 0.616 AC XY: 45648 AN XY: 74154

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.630

Alfa AF: 0.585 Hom.: 33486

Bravo AF: 0.639

Asia WGS AF: 0.495 AC: 1723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.72

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: rs12086738; hg19: chr1-65807412;