13-41192223-C-G

Variant summary

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

The NM_032138.7(KBTBD7):​c.2035G>C​(p.Asp679His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. D679Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

KBTBD7
NM_032138.7 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.864
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=0.10331324).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KBTBD7NM_032138.7 linkc.2035G>C p.Asp679His missense_variant Exon 1 of 1 ENST00000379483.4 NP_115514.2 Q8WVZ9
KBTBD6-DTNR_120423.1 linkn.350+29820C>G intron_variant Intron 3 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KBTBD7ENST00000379483.4 linkc.2035G>C p.Asp679His missense_variant Exon 1 of 1 6 NM_032138.7 ENSP00000368797.3 Q8WVZ9
ENSG00000278390ENST00000615685.4 linkn.320-417C>G intron_variant Intron 3 of 3 4
ENSG00000278390ENST00000619407.4 linkn.339+29820C>G intron_variant Intron 3 of 3 2
ENSG00000278390ENST00000661006.1 linkn.245+29820C>G intron_variant Intron 2 of 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.078
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
20
DANN
Uncertain
0.98
DEOGEN2
Benign
0.022
T
Eigen
Benign
-0.35
Eigen_PC
Benign
-0.19
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.70
T
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.75
T
MutationAssessor
Benign
0.55
N
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.14
N
REVEL
Benign
0.17
Sift
Benign
0.064
T
Sift4G
Benign
0.22
T
Polyphen
0.070
B
Vest4
0.21
MutPred
0.18
Loss of phosphorylation at S683 (P = 0.1042);
MVP
0.71
MPC
0.98
ClinPred
0.13
T
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.067
gMVP
0.24

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: rs771390802; hg19: chr13-41766359; API