NM_152246.3:c.1913A>G

Variant names:

• chr22-50571006-T-C
• NM_152246.3:c.1913A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152246.3(CPT1B):​c.1913A>G​(p.Lys638Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign 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: 3.45

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:41998): (CHKB-CPT1B readthrough (NMD candidate)) The genes CHKB and CPT1B are adjacent on chromosome 22 and read-through transcripts are expressed that include exons from both loci. The read-through transcripts are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to express proteins. [provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28572202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPT1B	NM_152246.3	c.1913A>G	p.Lys638Arg	missense_variant	Exon 16 of 20	ENST00000312108.12	NP_689452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPT1B	ENST00000312108.12	c.1913A>G	p.Lys638Arg	missense_variant	Exon 16 of 20	1	NM_152246.3	ENSP00000312189.8
CHKB-CPT1B	ENST00000453634.5	n.*2138A>G		non_coding_transcript_exon_variant	Exon 19 of 23	5		ENSP00000457031.1
CHKB-CPT1B	ENST00000453634.5	n.*2138A>G		3_prime_UTR_variant	Exon 19 of 23	5		ENSP00000457031.1

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

Jan 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1913A>G (p.K638R) alteration is located in exon 16 (coding exon 15) of the CPT1B gene. This alteration results from a A to G substitution at nucleotide position 1913, causing the lysine (K) at amino acid position 638 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	0.067
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T;T;T;T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.071
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.55	.;.;.;T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.29	T;T;T;T;T
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	1.3	L;L;L;L;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.94	N;N;N;N;N
REVEL	Uncertain	0.32
Sift	Uncertain	0.017	D;D;D;D;D
Sift4G	Benign	0.10	T;T;T;T;T
Polyphen		0.040	B;B;B;B;.
Vest4		0.20
MutPred		0.42		Gain of MoRF binding (P = 0.0938);Gain of MoRF binding (P = 0.0938);Gain of MoRF binding (P = 0.0938);Gain of MoRF binding (P = 0.0938);.;
MVP		0.89
ClinPred		0.40	T
GERP RS		5.6
Varity_R		0.13
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr22-51009435;