22-50569343-T-C

Variant names:

• chr22-50569343-T-C
• rs150762471
• NM_152246.3:c.2314A>G

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.2314A>G​(p.Ser772Gly) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S772R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CPT1B NM_152246.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.101751655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPT1B	NM_152246.3	c.2314A>G	p.Ser772Gly	missense_variant	Exon 19 of 20	ENST00000312108.12	NP_689452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPT1B	ENST00000312108.12	c.2314A>G	p.Ser772Gly	missense_variant	Exon 19 of 20	1	NM_152246.3	ENSP00000312189.8
CHKB-CPT1B	ENST00000453634.5	n.*2539A>G		non_coding_transcript_exon_variant	Exon 22 of 23	5		ENSP00000457031.1
CHKB-CPT1B	ENST00000453634.5	n.*2539A>G		3_prime_UTR_variant	Exon 22 of 23	5		ENSP00000457031.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T;T;T;T;.
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.37	.;.;.;T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.10	T;T;T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.69	N;N;N;N;.
PhyloP100		-0.21
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Benign	0.22
Sift	Uncertain	0.024	D;D;D;D;D
Sift4G	Benign	0.082	T;T;T;T;T
Polyphen		0.0	B;B;B;B;.
Vest4		0.18
MutPred		0.20		Gain of catalytic residue at P768 (P = 0.0945);Gain of catalytic residue at P768 (P = 0.0945);Gain of catalytic residue at P768 (P = 0.0945);Gain of catalytic residue at P768 (P = 0.0945);.;
MVP		0.79
ClinPred		0.23	T
GERP RS		1.7
Varity_R		0.068
gMVP		0.44
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs150762471; hg19: chr22-51007772;