1-65378971-T-G

Position:

• chr1-65378971-T-G

Variant summary

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

The NM_001256864.2(DNAJC6):​c.544-431T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,148 control chromosomes in the GnomAD database, including 8,268 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 0.25 (8268 hom., cov: 33)
• Consequence: DNAJC6 NM_001256864.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359

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 (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC6	NM_001256864.2	c.544-431T>G		intron_variant		ENST00000371069.5	NP_001243793.1
DNAJC6	NM_014787.4	c.373-431T>G		intron_variant			NP_055602.1
DNAJC6	NM_001256865.2	c.334-431T>G		intron_variant			NP_001243794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC6	ENST00000371069.5	c.544-431T>G		intron_variant		1	NM_001256864.2	ENSP00000360108.4

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37886 AN: 152030 Hom.: 8247 Cov.: 33

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0646

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.250 AC: 37966 AN: 152148 Hom.: 8268 Cov.: 33 AF XY: 0.256 AC XY: 19050 AN XY: 74394

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.0646

Gnomad4 OTH AF: 0.221

Alfa AF: 0.102 Hom.: 1541

Bravo AF: 0.268

Asia WGS AF: 0.477 AC: 1659 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	4.5
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: rs10493375; hg19: chr1-65844654;