1-65403591-C-T

Position:

• chr1-65403591-C-T

Variant summary

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

The ENST00000371069.5(DNAJC6):​c.2227+1711C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,018 control chromosomes in the GnomAD database, including 12,778 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 0.40 (12778 hom., cov: 32)
• Consequence: DNAJC6 ENST00000371069.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC6	NM_001256864.2	c.2227+1711C>T		intron_variant		ENST00000371069.5	NP_001243793.1
DNAJC6	NM_001256865.2	c.2017+1711C>T		intron_variant			NP_001243794.1
DNAJC6	NM_014787.4	c.2056+1711C>T		intron_variant			NP_055602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC6	ENST00000371069.5	c.2227+1711C>T		intron_variant		1	NM_001256864.2	ENSP00000360108	P4
DNAJC6	ENST00000395325.7	c.2056+1711C>T		intron_variant		1		ENSP00000378735	A1
DNAJC6	ENST00000263441.11	c.2017+1711C>T		intron_variant		2		ENSP00000263441	A1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60346 AN: 151902 Hom.: 12765 Cov.: 32

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.397 AC: 60385 AN: 152018 Hom.: 12778 Cov.: 32 AF XY: 0.399 AC XY: 29669 AN XY: 74324

Gnomad4 AFR AF: 0.520

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.374

Alfa AF: 0.341 Hom.: 16276

Bravo AF: 0.398

Asia WGS AF: 0.535 AC: 1860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.61

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: rs4655762; hg19: chr1-65869274;