NM_152246.3:c.2309C>T

Variant names:

• chr22-50569348-G-A
• rs1469762800
• NM_152246.3:c.2309C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152246.3(CPT1B):​c.2309C>T​(p.Ala770Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A770A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CPT1B NM_152246.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.826
• 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]

LOC107985568 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2309C>T	p.Ala770Val	missense	Exon 19 of 20	NP_689452.1	Q92523-1
	CPT1B	NM_001145135.2		c.2309C>T	p.Ala770Val	missense	Exon 19 of 20	NP_001138607.1	Q92523-1
	CPT1B	NM_001145137.2		c.2309C>T	p.Ala770Val	missense	Exon 18 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.2309C>T	p.Ala770Val	missense	Exon 19 of 20	ENSP00000312189.8	Q92523-1
	CPT1B	ENST00000395650.6	TSL:1	c.2309C>T	p.Ala770Val	missense	Exon 19 of 19	ENSP00000379011.2	Q92523-1
	CPT1B	ENST00000405237.7	TSL:1	c.2309C>T	p.Ala770Val	missense	Exon 18 of 19	ENSP00000385486.3	Q92523-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251162 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 2 AN: 1461784 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727192

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000447 AC: 2 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111972

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

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	0.080
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.83
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.17
Sift	Benign	0.16	T
Sift4G	Benign	0.13	T
Polyphen		0.044	B
Vest4		0.14
MutPred		0.18		Loss of helix (P = 0.0167)
MVP		0.76
ClinPred		0.026	T
GERP RS		2.8
Varity_R		0.029
gMVP		0.33
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.23		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1469762800; hg19: chr22-51007777;