22-50571509-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_152246.3(CPT1B):c.1606G>A(p.Val536Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000905 in 1,613,334 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000085 ( 1 hom. )
Consequence
CPT1B
NM_152246.3 missense
NM_152246.3 missense
Scores
7
11
Clinical Significance
Conservation
PhyloP100: 0.453
Genes affected
CPT1B (HGNC:2329): (carnitine palmitoyltransferase 1B) The protein encoded by this gene, a member of the carnitine/choline acetyltransferase family, is the rate-controlling enzyme of the long-chain fatty acid beta-oxidation pathway in muscle mitochondria. This enzyme is required for the net transport of long-chain fatty acyl-CoAs from the cytoplasm into the mitochondria. Multiple transcript variants encoding different isoforms have been found for this gene, and read-through transcripts are expressed from the upstream locus that include exons from this gene. [provided by RefSeq, Jun 2009]
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ACMG classification
Classification made for transcript
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=0.08795023).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPT1B | NM_152246.3 | c.1606G>A | p.Val536Met | missense_variant | 14/20 | ENST00000312108.12 | |
CHKB-CPT1B | NR_027928.2 | n.3176G>A | non_coding_transcript_exon_variant | 24/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPT1B | ENST00000312108.12 | c.1606G>A | p.Val536Met | missense_variant | 14/20 | 1 | NM_152246.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152182Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000161 AC: 40AN: 248432Hom.: 0 AF XY: 0.000104 AC XY: 14AN XY: 134606
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GnomAD4 exome AF: 0.0000849 AC: 124AN: 1461034Hom.: 1 Cov.: 32 AF XY: 0.0000702 AC XY: 51AN XY: 726824
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GnomAD4 genome ? AF: 0.000144 AC: 22AN: 152300Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74462
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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 | Jun 29, 2022 | The c.1606G>A (p.V536M) alteration is located in exon 14 (coding exon 13) of the CPT1B gene. This alteration results from a G to A substitution at nucleotide position 1606, causing the valine (V) at amino acid position 536 to be replaced by a methionine (M). 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
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D;D;D;D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;M;M;.
MutationTaster
Benign
D;D;D;D;D;D;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
D;D;D;D;.
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at