NM_152246.3:c.196A>T

Variant names:

• chr22-50577409-T-A
• rs3213445
• NM_152246.3:c.196A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152246.3(CPT1B):​c.196A>T​(p.Ile66Phe) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CPT1B NM_152246.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21
• Publications: 39 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14551595).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1B	NM_152246.3	MANE Select	c.196A>T	p.Ile66Phe	missense	Exon 3 of 20	NP_689452.1
	CPT1B	NM_001145135.2		c.196A>T	p.Ile66Phe	missense	Exon 3 of 20	NP_001138607.1
	CPT1B	NM_001145137.2		c.196A>T	p.Ile66Phe	missense	Exon 2 of 19	NP_001138609.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1B	ENST00000312108.12	TSL:1 MANE Select	c.196A>T	p.Ile66Phe	missense	Exon 3 of 20	ENSP00000312189.8
	CPT1B	ENST00000395650.6	TSL:1	c.196A>T	p.Ile66Phe	missense	Exon 3 of 19	ENSP00000379011.2
	CPT1B	ENST00000405237.7	TSL:1	c.196A>T	p.Ile66Phe	missense	Exon 2 of 19	ENSP00000385486.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	0.0081	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	17
DANN	Benign	0.84
DEOGEN2	Uncertain	0.57	D
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.73
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	-0.34	N
PhyloP100		2.2
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.24
Sift	Benign	0.28	T
Sift4G	Benign	0.18	T
Polyphen		0.14	B
Vest4		0.31
MutPred		0.38		Gain of catalytic residue at I66 (P = 0.0882)
MVP		0.49
ClinPred		0.29	T
GERP RS		0.88
Varity_R		0.096
gMVP		0.86
Mutation Taster		=86/14	polymorphism

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

dbSNP: rs3213445; hg19: chr22-51015838;