chr22-50571443-G-C

Position:

• chr22-50571443-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152246.3(CPT1B):​c.1672C>G​(p.Leu558Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CPT1B NM_152246.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.84

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]

CHKB-CPT1B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.752

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPT1B	NM_152246.3	c.1672C>G	p.Leu558Val	missense_variant	14/20	ENST00000312108.12	NP_689452.1
CHKB-CPT1B	NR_027928.2	n.3242C>G		non_coding_transcript_exon_variant	24/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPT1B	ENST00000312108.12	c.1672C>G	p.Leu558Val	missense_variant	14/20	1	NM_152246.3	ENSP00000312189	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Dec 03, 2021

The c.1672C>G (p.L558V) alteration is located in exon 14 (coding exon 13) of the CPT1B gene. This alteration results from a C to G substitution at nucleotide position 1672, causing the leucine (L) at amino acid position 558 to be replaced by a valine (V). 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	0.098
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D;D;D;D;.
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.73	.;.;.;T;T
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.75	D;D;D;D;D
MetaSVM	Uncertain	0.69	D
MutationAssessor	Uncertain	2.6	M;M;M;M;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.5	N;N;N;N;N
REVEL	Pathogenic	0.67
Sift	Uncertain	0.028	D;D;D;D;D
Sift4G	Benign	0.13	T;T;T;T;T
Polyphen		0.97	D;D;D;D;.
Vest4		0.60
MutPred		0.74		Gain of methylation at K560 (P = 0.0792);Gain of methylation at K560 (P = 0.0792);Gain of methylation at K560 (P = 0.0792);Gain of methylation at K560 (P = 0.0792);.;
MVP		0.93
ClinPred		0.80	D
GERP RS		5.3
Varity_R		0.35
gMVP		0.56

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: chr22-51009872;