13-41192223-C-G

Variant names:

• chr13-41192223-C-G
• rs771390802
• NM_032138.7:c.2035G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.864

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)

ACMG classification

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
KBTBD7	NM_032138.7	c.2035G>C	p.Asp679His	missense_variant	Exon 1 of 1	ENST00000379483.4	NP_115514.2
KBTBD6-DT	NR_120423.1	n.350+29820C>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KBTBD7	ENST00000379483.4	c.2035G>C	p.Asp679His	missense_variant	Exon 1 of 1	6	NM_032138.7	ENSP00000368797.3
ENSG00000278390	ENST00000615685.4	n.320-417C>G		intron_variant	Intron 3 of 3	4
ENSG00000278390	ENST00000619407.4	n.339+29820C>G		intron_variant	Intron 3 of 3	2
ENSG00000278390	ENST00000661006.1	n.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

Other links and lift over

dbSNP: rs771390802; hg19: chr13-41766359;