11-47573229-C-T

Variant summary

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

The NM_018095.6(KBTBD4):​c.1306G>A​(p.Ala436Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KBTBD4
NM_018095.6 missense

Scores

3
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57
Variant links:
Genes affected
KBTBD4 (HGNC:23761): (kelch repeat and BTB domain containing 4)
PTPMT1 (HGNC:26965): (protein tyrosine phosphatase mitochondrial 1) Predicted to enable phosphatidylglycerophosphatase activity and phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity. Involved in regulation of intrinsic apoptotic signaling pathway. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
KBTBD4NM_018095.6 linkuse as main transcriptc.1306G>A p.Ala436Thr missense_variant 4/4 ENST00000430070.7 NP_060565.4 Q9NVX7-2
PTPMT1NM_175732.3 linkuse as main transcriptc.*1600C>T 3_prime_UTR_variant 4/4 ENST00000326674.10 NP_783859.1 Q8WUK0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KBTBD4ENST00000430070.7 linkuse as main transcriptc.1306G>A p.Ala436Thr missense_variant 4/41 NM_018095.6 ENSP00000415106.2 Q9NVX7-2
PTPMT1ENST00000326674.10 linkuse as main transcriptc.*1600C>T 3_prime_UTR_variant 4/41 NM_175732.3 ENSP00000325958.9 Q8WUK0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461890
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727246
show subpopulations
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 29, 2024The c.1306G>A (p.A436T) alteration is located in exon 4 (coding exon 4) of the KBTBD4 gene. This alteration results from a G to A substitution at nucleotide position 1306, causing the alanine (A) at amino acid position 436 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
0.24
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
CADD
Uncertain
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.043
T;T;T;.
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.96
D
M_CAP
Benign
0.058
D
MetaRNN
Uncertain
0.68
D;D;D;D
MetaSVM
Benign
-0.31
T
MutationAssessor
Benign
0.79
N;.;N;.
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-0.36
N;N;N;N
REVEL
Uncertain
0.33
Sift
Benign
0.083
T;T;T;T
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0
D;.;D;D
Vest4
0.77
MutPred
0.48
Loss of sheet (P = 0.1501);.;Loss of sheet (P = 0.1501);.;
MVP
0.84
MPC
0.93
ClinPred
0.85
D
GERP RS
5.1
Varity_R
0.22
gMVP
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chr11-47594781; API