7-87349112-A-G

Variant summary

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

The NM_021151.4(CROT):c.44A>G(p.Gln15Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CROT NM_021151.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.77

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]

ACMG classification

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.44A>G	p.Gln15Arg	missense_variant	3/18	ENST00000331536.8
CROT	NM_001143935.2	c.44A>G	p.Gln15Arg	missense_variant	3/19
CROT	NM_001243745.3	c.44A>G	p.Gln15Arg	missense_variant	3/4
CROT	XM_011516337.4	c.44A>G	p.Gln15Arg	missense_variant	3/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CROT	ENST00000331536.8	c.44A>G	p.Gln15Arg	missense_variant	3/18	1	NM_021151.4	P1
CROT	ENST00000412227.6	c.44A>G	p.Gln15Arg	missense_variant	3/4	1
CROT	ENST00000419147.6	c.44A>G	p.Gln15Arg	missense_variant	3/19	2
CROT	ENST00000442291.1	c.44A>G	p.Gln15Arg	missense_variant	2/17	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 06, 2023

The c.44A>G (p.Q15R) alteration is located in exon 3 (coding exon 1) of the CROT gene. This alteration results from a A to G substitution at nucleotide position 44, causing the glutamine (Q) at amino acid position 15 to be replaced by an arginine (R). 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	0.27	D
BayesDel_noAF	Pathogenic	0.16
Cadd	Uncertain	23
Dann	Uncertain	0.99
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.85	T;T;T;T
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.49	T;T;T;T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	1.1	L;L;L;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Uncertain	0.46
Sift	Uncertain	0.024	D;T;T;T
Sift4G	Benign	0.11	T;T;T;T
Polyphen		0.52	.;.;P;.
Vest4		0.63
MutPred		0.20		Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.73
MPC		0.075
ClinPred		0.83	D
GERP RS		5.8
Varity_R		0.35
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-86978428;