13-41192513-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032138.7(KBTBD7):​c.1745G>A​(p.Arg582Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

KBTBD7
NM_032138.7 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.40
Variant links:
Genes affected
KBTBD7 (HGNC:25266): (kelch repeat and BTB domain containing 7) The protein encoded by this gene is a transcriptional activator, having been shown to increase the transcription of activator protein-1 and serum response element. The encoded protein can also form a complex with KBTBD6 and CUL3, which regulates the ubiquitylation and degradation of TIAM1, which is a regulator of RAC1. [provided by RefSeq, Jul 2016]
ENSG00000278390 (HGNC:56824): (KBTBD6 divergent transcript)

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ACMG classification

Classification made for transcript

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=0.22299138).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KBTBD7NM_032138.7 linkc.1745G>A p.Arg582Gln missense_variant Exon 1 of 1 ENST00000379483.4 NP_115514.2 Q8WVZ9
KBTBD6-DTNR_120423.1 linkn.350+30110C>T intron_variant Intron 3 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KBTBD7ENST00000379483.4 linkc.1745G>A p.Arg582Gln missense_variant Exon 1 of 1 6 NM_032138.7 ENSP00000368797.3 Q8WVZ9
ENSG00000278390ENST00000615685.4 linkn.320-127C>T intron_variant Intron 3 of 3 4
ENSG00000278390ENST00000619407.4 linkn.339+30110C>T intron_variant Intron 3 of 3 2
ENSG00000278390ENST00000661006.1 linkn.245+30110C>T intron_variant Intron 2 of 2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251446
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461858
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00000719
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 26, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1745G>A (p.R582Q) alteration is located in exon 1 (coding exon 1) of the KBTBD7 gene. This alteration results from a G to A substitution at nucleotide position 1745, causing the arginine (R) at amino acid position 582 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Uncertain
0.047
T
BayesDel_noAF
Benign
-0.090
CADD
Benign
22
DANN
Benign
0.95
DEOGEN2
Benign
0.035
T
Eigen
Benign
-0.19
Eigen_PC
Benign
-0.080
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.86
D
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.22
T
MetaSVM
Benign
-0.72
T
MutationAssessor
Benign
0.89
L
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-0.63
N
REVEL
Uncertain
0.36
Sift
Uncertain
0.023
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.41
B
Vest4
0.39
MVP
0.78
MPC
0.81
ClinPred
0.29
T
GERP RS
4.7
Varity_R
0.22
gMVP
0.28

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: rs772795656; hg19: chr13-41766649; COSMIC: COSV104432714; COSMIC: COSV104432714; API