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GeneBe

3-128463228-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_153330.6(DNAJB8):c.18A>G(p.Glu6=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00263 in 1,612,514 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 42 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 43 hom. )

Consequence

DNAJB8
NM_153330.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.35
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-128463228-T-C is Benign according to our data. Variant chr3-128463228-T-C is described in ClinVar as [Benign]. Clinvar id is 789713.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.35 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0141 (2141/152176) while in subpopulation AFR AF= 0.0472 (1961/41538). AF 95% confidence interval is 0.0455. There are 42 homozygotes in gnomad4. There are 1062 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 42 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DNAJB8NM_153330.6 linkuse as main transcriptc.18A>G p.Glu6= synonymous_variant 3/3 ENST00000319153.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DNAJB8ENST00000319153.4 linkuse as main transcriptc.18A>G p.Glu6= synonymous_variant 3/31 NM_153330.6 P1
DNAJB8ENST00000469083.1 linkuse as main transcriptc.18A>G p.Glu6= synonymous_variant 2/22 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0141
AC:
2139
AN:
152058
Hom.:
42
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0473
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00923
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.0110
GnomAD3 exomes
AF:
0.00373
AC:
934
AN:
250222
Hom.:
25
AF XY:
0.00289
AC XY:
391
AN XY:
135284
show subpopulations
Gnomad AFR exome
AF:
0.0495
Gnomad AMR exome
AF:
0.00333
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000531
Gnomad OTH exome
AF:
0.00197
GnomAD4 exome
AF:
0.00144
AC:
2104
AN:
1460338
Hom.:
43
Cov.:
38
AF XY:
0.00127
AC XY:
922
AN XY:
726260
show subpopulations
Gnomad4 AFR exome
AF:
0.0492
Gnomad4 AMR exome
AF:
0.00392
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000163
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000378
Gnomad4 OTH exome
AF:
0.00360
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0141
AC:
2141
AN:
152176
Hom.:
42
Cov.:
32
AF XY:
0.0143
AC XY:
1062
AN XY:
74400
show subpopulations
Gnomad4 AFR
AF:
0.0472
Gnomad4 AMR
AF:
0.00922
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.0109
Alfa
AF:
0.00716
Hom.:
16
Bravo
AF:
0.0167
Asia WGS
AF:
0.00404
AC:
14
AN:
3478
EpiCase
AF:
0.0000546
EpiControl
AF:
0.000119

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 submitterclinical testingInvitaeJun 18, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
Cadd
Benign
2.1
Dann
Benign
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs13326637; hg19: chr3-128182071; API