rs78141380

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000371069.5(DNAJC6):ā€‹c.1456C>Gā€‹(p.Leu486Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L486F) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

DNAJC6
ENST00000371069.5 missense

Scores

10
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.69
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36898834).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAJC6NM_001256864.2 linkuse as main transcriptc.1456C>G p.Leu486Val missense_variant 11/19 ENST00000371069.5 NP_001243793.1
DNAJC6NM_014787.4 linkuse as main transcriptc.1285C>G p.Leu429Val missense_variant 11/19 NP_055602.1
DNAJC6NM_001256865.2 linkuse as main transcriptc.1246C>G p.Leu416Val missense_variant 12/20 NP_001243794.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAJC6ENST00000371069.5 linkuse as main transcriptc.1456C>G p.Leu486Val missense_variant 11/191 NM_001256864.2 ENSP00000360108 P4O75061-2
DNAJC6ENST00000395325.7 linkuse as main transcriptc.1285C>G p.Leu429Val missense_variant 11/191 ENSP00000378735 A1O75061-1
DNAJC6ENST00000263441.11 linkuse as main transcriptc.1246C>G p.Leu416Val missense_variant 12/202 ENSP00000263441 A1O75061-4
DNAJC6ENST00000494710.6 linkuse as main transcriptc.1378C>G p.Leu460Val missense_variant 11/125 ENSP00000473821

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461782
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727192
show subpopulations
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:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
.;.;T;.
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.94
D;D;D;D
M_CAP
Benign
0.073
D
MetaRNN
Benign
0.37
T;T;T;T
MetaSVM
Uncertain
0.40
D
MutationAssessor
Uncertain
2.3
.;.;M;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.6
.;N;N;N
REVEL
Uncertain
0.46
Sift
Benign
0.098
.;T;D;T
Sift4G
Benign
0.11
T;T;T;T
Polyphen
0.94, 0.99
.;.;P;D
Vest4
0.29, 0.28, 0.25
MutPred
0.38
.;.;Gain of helix (P = 0.0082);.;
MVP
0.58
MPC
0.31
ClinPred
0.93
D
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.17
gMVP
0.40

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs78141380; hg19: chr1-65855298; API