chr13-41192472-T-G

Variant names:

• chr13-41192472-T-G
• rs368581328
• NM_032138.7:c.1786A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032138.7(KBTBD7):​c.1786A>C​(p.Ile596Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,614,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: KBTBD7 NM_032138.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.643
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.044700414).

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.1786A>C	p.Ile596Leu	missense	Exon 1 of 1	NP_115514.2
	KBTBD6-DT	NR_120423.1		n.350+30069T>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.1786A>C	p.Ile596Leu	missense	Exon 1 of 1	ENSP00000368797.3	Q8WVZ9
	KBTBD6-DT	ENST00000615685.4	TSL:4	n.320-168T>G		intron	N/A
	KBTBD6-DT	ENST00000619407.4	TSL:2	n.339+30069T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152224 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000517 AC: 13 AN: 251448 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000738

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 727244

African (AFR) AF: 0.000806 AC: 27 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

Other (OTH) AF: 0.0000497 AC: 3 AN: 60396

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152224 Hom.: 0 Cov.: 31 AF XY: 0.000229 AC XY: 17 AN XY: 74374

African (AFR) AF: 0.000603 AC: 25 AN: 41452

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000579 Hom.: 0

Bravo AF: 0.000155

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000576 AC: 7

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	0.10
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.85
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.64
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.035
Sift	Benign	0.58	T
Sift4G	Benign	0.51	T
Polyphen		0.0010	B
Vest4		0.17
MVP		0.50
MPC		0.68
ClinPred		0.023	T
GERP RS		1.7
Varity_R		0.079
gMVP		0.096
Mutation Taster		=70/30	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: rs368581328; hg19: chr13-41766608;