13-41192634-C-G

Variant names:

• chr13-41192634-C-G
• NM_032138.7:c.1624G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032138.7(KBTBD7):​c.1624G>C​(p.Gly542Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KBTBD7 NM_032138.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.40

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KBTBD7	NM_032138.7	c.1624G>C	p.Gly542Arg	missense_variant	Exon 1 of 1	ENST00000379483.4	NP_115514.2
KBTBD6-DT	NR_120423.1	n.350+30231C>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KBTBD7	ENST00000379483.4	c.1624G>C	p.Gly542Arg	missense_variant	Exon 1 of 1	6	NM_032138.7	ENSP00000368797.3
ENSG00000278390	ENST00000615685.4	n.320-6C>G		splice_region_variant, intron_variant	Intron 3 of 3	4
ENSG00000278390	ENST00000619407.4	n.339+30231C>G		intron_variant	Intron 3 of 3	2
ENSG00000278390	ENST00000661006.1	n.245+30231C>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1624G>C (p.G542R) alteration is located in exon 1 (coding exon 1) of the KBTBD7 gene. This alteration results from a G to C substitution at nucleotide position 1624, causing the glycine (G) at amino acid position 542 to be replaced by an arginine (R). 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	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.8	L
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.36
Sift	Benign	0.075	T
Sift4G	Uncertain	0.0050	D
Polyphen		0.89	P
Vest4		0.54
MutPred		0.52		Gain of MoRF binding (P = 0.011);
MVP		0.88
MPC		1.7
ClinPred		0.96	D
GERP RS		5.4
Varity_R		0.38
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-41766770;