Variant 7-87361762-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_021151.4(CROT):c.457C>A(p.Pro153Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CROT
NM_021151.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.65

Variant links:

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]

CROT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.883

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CROT	NM_021151.4 linkuse as main transcript	c.457C>A	p.Pro153Thr	missense_variant	6/18	ENST00000331536.8
CROT	NM_001143935.2 linkuse as main transcript	c.541C>A	p.Pro181Thr	missense_variant	7/19
CROT	XM_011516337.4 linkuse as main transcript	c.457C>A	p.Pro153Thr	missense_variant	6/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CROT	ENST00000331536.8 linkuse as main transcript	c.457C>A	p.Pro153Thr	missense_variant	6/18	1	NM_021151.4	P1	Q9UKG9-1
CROT	ENST00000419147.6 linkuse as main transcript	c.541C>A	p.Pro181Thr	missense_variant	7/19	2			Q9UKG9-3
CROT	ENST00000442291.1 linkuse as main transcript	c.457C>A	p.Pro153Thr	missense_variant	5/17	5
CROT	ENST00000488850.1 linkuse as main transcript	n.164C>A		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245546

Hom.:

AF XY:

0.00000754

AC XY:

AN XY:

132576

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000348

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1453446

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722716

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:

9.02e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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 26, 2022

The c.541C>A (p.P181T) alteration is located in exon 7 (coding exon 5) of the CROT gene. This alteration results from a C to A substitution at nucleotide position 541, causing the proline (P) at amino acid position 181 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

0.17

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.15

Cadd

Benign

Dann

Uncertain

0.98

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.058

MetaRNN

Pathogenic

0.88

D;D;D

MetaSVM

Uncertain

0.60

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Pathogenic

0.69

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.24

T;T;T

Polyphen

0.11

.;B;.

Vest4

0.73

MutPred

0.83

.;Gain of catalytic residue at P153 (P = 0.0863);Gain of catalytic residue at P153 (P = 0.0863);

MVP

0.82

MPC

0.079

ClinPred

0.92

GERP RS

5.6

Varity_R

0.31

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over