8-2001631-T-C

Position:

• chr8-2001631-T-C

Variant summary

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

The ENST00000320248.4(KBTBD11):​c.439T>C​(p.Ser147Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S147W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KBTBD11 ENST00000320248.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.856

Genes affected

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

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/exons	MANE	Protein	UniProt
KBTBD11	NM_014867.3	c.439T>C	p.Ser147Pro	missense_variant	2/2	ENST00000320248.4	NP_055682.1
KBTBD11	XM_011534772.3	c.439T>C	p.Ser147Pro	missense_variant	3/3		XP_011533074.1
KBTBD11	XM_017014116.2	c.439T>C	p.Ser147Pro	missense_variant	3/3		XP_016869605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KBTBD11	ENST00000320248.4	c.439T>C	p.Ser147Pro	missense_variant	2/2	1	NM_014867.3	ENSP00000321544	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1327986 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 655548

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: 0.00

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

Jun 29, 2023

The c.439T>C (p.S147P) alteration is located in exon 2 (coding exon 1) of the KBTBD11 gene. This alteration results from a T to C substitution at nucleotide position 439, causing the serine (S) at amino acid position 147 to be replaced by a proline (P). 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	Uncertain	0.50
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.49	N
M_CAP	Pathogenic	0.85	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.15
Sift	Benign	0.14	T
Sift4G	Benign	0.069	T
Polyphen		0.87	P
Vest4		0.21
MutPred		0.49		Loss of glycosylation at S147 (P = 0.0152);
MVP		0.80
MPC		2.3
ClinPred		0.30	T
GERP RS		-0.69
Varity_R		0.072
gMVP		0.57

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: chr8-1949797;