NM_152246.3:c.2077C>G

Variant names:

• chr22-50570358-G-C
• NM_152246.3:c.2077C>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_152246.3(CPT1B):​c.2077C>G​(p.Gln693Glu) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 9.55
• Publications: 0 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.96

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152246.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1B	NM_152246.3	MANE Select	c.2077C>G	p.Gln693Glu	missense	Exon 17 of 20	NP_689452.1	Q92523-1
	CPT1B	NM_001145135.2		c.2077C>G	p.Gln693Glu	missense	Exon 17 of 20	NP_001138607.1	Q92523-1
	CPT1B	NM_001145137.2		c.2077C>G	p.Gln693Glu	missense	Exon 16 of 19	NP_001138609.1	Q92523-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1B	ENST00000312108.12	TSL:1 MANE Select	c.2077C>G	p.Gln693Glu	missense	Exon 17 of 20	ENSP00000312189.8	Q92523-1
	CPT1B	ENST00000395650.6	TSL:1	c.2077C>G	p.Gln693Glu	missense	Exon 17 of 19	ENSP00000379011.2	Q92523-1
	CPT1B	ENST00000405237.7	TSL:1	c.2077C>G	p.Gln693Glu	missense	Exon 16 of 19	ENSP00000385486.3	Q92523-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.76	D
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	0.74	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		9.6
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.3	N
REVEL	Pathogenic	0.86
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.030	D
Polyphen		0.68	P
Vest4		0.64
MutPred		0.84		Gain of disorder (P = 0.1327)
MVP		0.96
ClinPred		0.98	D
GERP RS		5.4
Varity_R		0.54
gMVP		0.84
Mutation Taster		=45/55	disease causing

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

Other links and lift over

hg19: chr22-51008787;