rs886039854

Variant names:

• chr1-65408685-C-A
• NM_001256864.2:c.2536C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-65408685-C-A
• chr1-65408685-C-G
• chr1-65408685-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001256864.2(DNAJC6):​c.2536C>A​(p.Gln846Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,692 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DNAJC6 NM_001256864.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC6	NM_001256864.2	c.2536C>A	p.Gln846Lys	missense_variant	Exon 17 of 19	ENST00000371069.5	NP_001243793.1
DNAJC6	NM_014787.4	c.2365C>A	p.Gln789Lys	missense_variant	Exon 17 of 19		NP_055602.1
DNAJC6	NM_001256865.2	c.2326C>A	p.Gln776Lys	missense_variant	Exon 18 of 20		NP_001243794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC6	ENST00000371069.5	c.2536C>A	p.Gln846Lys	missense_variant	Exon 17 of 19	1	NM_001256864.2	ENSP00000360108.4
DNAJC6	ENST00000395325.7	c.2365C>A	p.Gln789Lys	missense_variant	Exon 17 of 19	1		ENSP00000378735.3
DNAJC6	ENST00000263441.11	c.2326C>A	p.Gln776Lys	missense_variant	Exon 18 of 20	2		ENSP00000263441.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461692 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727150

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.73	.;D;.
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.8	.;M;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Benign	0.25
Sift	Benign	0.045	D;D;D
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		0.95, 0.97	.;P;D
Vest4		0.61
MutPred		0.30		.;Gain of ubiquitination at Q789 (P = 0.0025);.;
MVP		0.49
MPC		1.0
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.63
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-65874368;