NM_032138.7:c.1373G>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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.1373G>C	p.Ser458Thr	missense_variant	Exon 1 of 1	ENST00000379483.4	NP_115514.2
KBTBD6-DT	NR_120423.1	n.350+30482C>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KBTBD7	ENST00000379483.4	c.1373G>C	p.Ser458Thr	missense_variant	Exon 1 of 1	6	NM_032138.7	ENSP00000368797.3
ENSG00000278390	ENST00000619407.4	n.339+30482C>G		intron_variant	Intron 3 of 3	2
ENSG00000278390	ENST00000661006.1	n.245+30482C>G		intron_variant	Intron 2 of 2
ENSG00000278390	ENST00000615685.4	n.*50C>G		downstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 28, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1373G>C (p.S458T) 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 1373, causing the serine (S) at amino acid position 458 to be replaced by a threonine (T). 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	0.31
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
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

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: chr13-41767021;