chr1-65309926-A-G

Variant names:

• chr1-65309926-A-G
• NM_001256864.2:c.181A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001256864.2(DNAJC6):​c.181A>G​(p.Met61Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: DNAJC6 NM_001256864.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.58

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1191155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC6	NM_001256864.2	c.181A>G	p.Met61Val	missense_variant	Exon 1 of 19	ENST00000371069.5	NP_001243793.1
DNAJC6	NM_014787.4	c.22+44994A>G		intron_variant	Intron 1 of 18		NP_055602.1
DNAJC6	NM_001256865.2	c.-130-35685A>G		intron_variant	Intron 1 of 19		NP_001243794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC6	ENST00000371069.5	c.181A>G	p.Met61Val	missense_variant	Exon 1 of 19	1	NM_001256864.2	ENSP00000360108.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

May 30, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.0077	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	20
DANN	Benign	0.93
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.46	T
M_CAP	Pathogenic	0.67	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.78	T
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.16	N
REVEL	Uncertain	0.30
Sift	Benign	1.0	T
Sift4G	Benign	0.65	T
Polyphen		0.0010	B
Vest4		0.15
MutPred		0.092		Gain of glycosylation at S63 (P = 0.144);
MVP		0.39
MPC		0.27
ClinPred		0.49	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-65775609;