7-87381968-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_021151.4(CROT):c.1037T>G(p.Ile346Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,609,624 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
CROT
NM_021151.4 missense
NM_021151.4 missense
Scores
2
8
7
Clinical Significance
Conservation
PhyloP100: 7.40
Genes affected
CROT (HGNC:2366): (carnitine O-octanoyltransferase) This gene encodes a member of the carnitine/choline acetyltransferase family. The encoded protein converts 4,8-dimethylnonanoyl-CoA to its corresponding carnitine ester. This transesterification occurs in the peroxisome and is necessary for transport of medium- and long- chain acyl-CoA molecules out of the peroxisome to the cytosol and mitochondria. The protein thus plays a role in lipid metabolism and fatty acid beta-oxidation. Alternatively spliced transcript variants have been described.[provided by RefSeq, Jan 2009]
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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 | UniProt |
---|---|---|---|---|---|---|---|
CROT | NM_021151.4 | c.1037T>G | p.Ile346Ser | missense_variant | 11/18 | ENST00000331536.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CROT | ENST00000331536.8 | c.1037T>G | p.Ile346Ser | missense_variant | 11/18 | 1 | NM_021151.4 | P1 | |
CROT | ENST00000419147.6 | c.1121T>G | p.Ile374Ser | missense_variant | 12/19 | 2 | |||
CROT | ENST00000442291.1 | c.1037T>G | p.Ile346Ser | missense_variant | 10/17 | 5 | |||
CROT | ENST00000479014.1 | n.242T>G | non_coding_transcript_exon_variant | 3/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152130Hom.: 0 Cov.: 33
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?
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GnomAD3 exomes AF: 0.0000520 AC: 13AN: 249880Hom.: 0 AF XY: 0.0000518 AC XY: 7AN XY: 135026
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GnomAD4 exome AF: 0.0000110 AC: 16AN: 1457376Hom.: 0 Cov.: 28 AF XY: 0.00000966 AC XY: 7AN XY: 724964
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74438
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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 | Mar 29, 2022 | The c.1121T>G (p.I374S) alteration is located in exon 12 (coding exon 10) of the CROT gene. This alteration results from a T to G substitution at nucleotide position 1121, causing the isoleucine (I) at amino acid position 374 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
0.46
.;P;.
Vest4
MutPred
0.64
.;Gain of disorder (P = 0.0016);Gain of disorder (P = 0.0016);
MVP
MPC
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