11-47573229-C-T
Position:
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
NM_018095.6 missense
Scores
3
7
8
Clinical Significance
Conservation
PhyloP100: 7.57
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]
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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 |
---|---|---|---|---|---|---|---|---|
KBTBD4 | NM_018095.6 | c.1306G>A | p.Ala436Thr | missense_variant | 4/4 | ENST00000430070.7 | NP_060565.4 | |
PTPMT1 | NM_175732.3 | c.*1600C>T | 3_prime_UTR_variant | 4/4 | ENST00000326674.10 | NP_783859.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KBTBD4 | ENST00000430070.7 | c.1306G>A | p.Ala436Thr | missense_variant | 4/4 | 1 | NM_018095.6 | ENSP00000415106.2 | ||
PTPMT1 | ENST00000326674.10 | c.*1600C>T | 3_prime_UTR_variant | 4/4 | 1 | NM_175732.3 | ENSP00000325958.9 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461890Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727246
GnomAD4 exome
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3
AN:
1461890
Hom.:
Cov.:
31
AF XY:
AC XY:
3
AN XY:
727246
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
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 submitter | clinical testing | Ambry Genetics | Oct 29, 2024 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;N;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T
Sift4G
Pathogenic
D;D;D;D
Polyphen
D;.;D;D
Vest4
MutPred
Loss of sheet (P = 0.1501);.;Loss of sheet (P = 0.1501);.;
MVP
MPC
0.93
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.