7-87369468-C-A

Variant summary

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

The NM_021151.4(CROT):c.640C>A(p.Pro214Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,610,968 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., 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: 3.39

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:

ABCB4 (HGNC:):

ABCB4 links:

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
CROT	NM_021151.4 linkuse as main transcript	c.640C>A	p.Pro214Thr	missense_variant	7/18	ENST00000331536.8
CROT	NM_001143935.2 linkuse as main transcript	c.724C>A	p.Pro242Thr	missense_variant	8/19
CROT	XM_011516337.4 linkuse as main transcript	c.640C>A	p.Pro214Thr	missense_variant	7/18
ABCB4	XR_007060054.1 linkuse as main transcript	n.3866-716G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CROT	ENST00000331536.8 linkuse as main transcript	c.640C>A	p.Pro214Thr	missense_variant	7/18	1	NM_021151.4	P1	Q9UKG9-1
CROT	ENST00000419147.6 linkuse as main transcript	c.724C>A	p.Pro242Thr	missense_variant	8/19	2			Q9UKG9-3
CROT	ENST00000442291.1 linkuse as main transcript	c.640C>A	p.Pro214Thr	missense_variant	6/17	5
CROT	ENST00000488850.1 linkuse as main transcript	n.347C>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250710

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135572

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458726

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725852

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Dec 14, 2021

The c.724C>A (p.P242T) alteration is located in exon 8 (coding exon 6) of the CROT gene. This alteration results from a C to A substitution at nucleotide position 724, causing the proline (P) at amino acid position 242 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

Uncertain

0.40

BayesDel_addAF

Benign

0.00046

BayesDel_noAF

Uncertain

-0.060

Cadd

Uncertain

Dann

Uncertain

0.99

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.74

D;D;D

MetaSVM

Uncertain

0.55

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-4.5

D;D;D

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.016

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.64

MutPred

0.63

.;Loss of stability (P = 0.0936);Loss of stability (P = 0.0936);

MVP

0.78

MPC

0.20

ClinPred

0.97

GERP RS

3.3

Varity_R

0.65

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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