chr13-41192885-C-G

Variant names:

• chr13-41192885-C-G
• rs2031427496
• NM_032138.7:c.1373G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032138.7(KBTBD7):​c.1373G>C​(p.Ser458Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KBTBD7 NM_032138.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.41
• Publications: 0 publications found

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]

KBTBD6-DT (HGNC:56824): (KBTBD6 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032138.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KBTBD7	NM_032138.7	MANE Select	c.1373G>C	p.Ser458Thr	missense	Exon 1 of 1	NP_115514.2
	KBTBD6-DT	NR_120423.1		n.350+30482C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KBTBD7	ENST00000379483.4	TSL:6 MANE Select	c.1373G>C	p.Ser458Thr	missense	Exon 1 of 1	ENSP00000368797.3	Q8WVZ9
	KBTBD6-DT	ENST00000619407.4	TSL:2	n.339+30482C>G		intron	N/A
	KBTBD6-DT	ENST00000661006.1		n.245+30482C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.34	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.093	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.4
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.57
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.042	D
Polyphen		0.83	P
Vest4		0.26
MutPred		0.84		Gain of phosphorylation at S458 (P = 0.2393)
MVP		0.84
MPC		1.2
ClinPred		0.76	D
GERP RS		4.7
Varity_R		0.44
gMVP		0.77
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs2031427496; hg19: chr13-41767021;