8-2001415-G-A

Position:

• chr8-2001415-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000320248.4(KBTBD11):​c.223G>A​(p.Glu75Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000806 in 1,240,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: KBTBD11 ENST00000320248.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.946

Genes affected

KBTBD11 (HGNC:29104): (kelch repeat and BTB domain containing 11)

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=0.15462652).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KBTBD11	NM_014867.3	c.223G>A	p.Glu75Lys	missense_variant	2/2	ENST00000320248.4	NP_055682.1
KBTBD11	XM_011534772.3	c.223G>A	p.Glu75Lys	missense_variant	3/3		XP_011533074.1
KBTBD11	XM_017014116.2	c.223G>A	p.Glu75Lys	missense_variant	3/3		XP_016869605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KBTBD11	ENST00000320248.4	c.223G>A	p.Glu75Lys	missense_variant	2/2	1	NM_014867.3	ENSP00000321544	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.06e-7 AC: 1 AN: 1240926 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 606686

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.89e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.223G>A (p.E75K) alteration is located in exon 2 (coding exon 1) of the KBTBD11 gene. This alteration results from a G to A substitution at nucleotide position 223, causing the glutamic acid (E) at amino acid position 75 to be replaced by a lysine (K). 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	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.1
DANN	Benign	0.93
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.018	N
M_CAP	Pathogenic	0.87	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.81	L
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.16
Sift	Benign	0.33	T
Sift4G	Benign	0.28	T
Polyphen		0.0	B
Vest4		0.073
MutPred		0.34		Gain of MoRF binding (P = 0.0022);
MVP		0.40
MPC		1.2
ClinPred		0.087	T
GERP RS		-4.9
Varity_R		0.080
gMVP		0.13

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: chr8-1949581;