chr3-128462944-C-T
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_153330.6(DNAJB8):c.302G>A(p.Arg101Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,614,092 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0072 ( 12 hom., cov: 32)
Exomes 𝑓: 0.00077 ( 5 hom. )
Consequence
DNAJB8
NM_153330.6 missense
NM_153330.6 missense
Scores
7
10
Clinical Significance
Conservation
PhyloP100: 1.72
Genes affected
DNAJB8 (HGNC:23699): (DnaJ heat shock protein family (Hsp40) member B8) The protein encoded by this gene belongs to the DNAJ/HSP40 family of proteins that regulate chaperone activity. This family member suppresses aggregation and toxicity of polyglutamine proteins, and the C-terminal tail is essential for this activity. It has been implicated as a cancer-testis antigen and as a cancer stem-like cell antigen involved in renal cell carcinoma. [provided by RefSeq, Jun 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.007894695).
BP6
Variant 3-128462944-C-T is Benign according to our data. Variant chr3-128462944-C-T is described in ClinVar as [Benign]. Clinvar id is 767931.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00717 (1092/152282) while in subpopulation AFR AF= 0.0247 (1027/41558). AF 95% confidence interval is 0.0235. There are 12 homozygotes in gnomad4. There are 504 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 12 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAJB8 | NM_153330.6 | c.302G>A | p.Arg101Gln | missense_variant | 3/3 | ENST00000319153.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAJB8 | ENST00000319153.4 | c.302G>A | p.Arg101Gln | missense_variant | 3/3 | 1 | NM_153330.6 | P1 | |
DNAJB8 | ENST00000469083.1 | c.302G>A | p.Arg101Gln | missense_variant | 2/2 | 2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00717 AC: 1091AN: 152164Hom.: 12 Cov.: 32
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GnomAD3 exomes AF: 0.00179 AC: 450AN: 250782Hom.: 2 AF XY: 0.00118 AC XY: 160AN XY: 135628
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GnomAD4 exome AF: 0.000772 AC: 1129AN: 1461810Hom.: 5 Cov.: 38 AF XY: 0.000608 AC XY: 442AN XY: 727204
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GnomAD4 genome AF: 0.00717 AC: 1092AN: 152282Hom.: 12 Cov.: 32 AF XY: 0.00677 AC XY: 504AN XY: 74458
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jun 18, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
ClinPred
T
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at