rs930693952

Variant names:

• chr5-71719901-T-A
• rs930693952
• NM_004291.4:c.181T>A
• CARTPT p.Leu61Met

Your query was ambiguous. Multiple possible variants found:

• chr5-71719901-T-A
• chr5-71719901-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004291.4(CARTPT):​c.181T>A​(p.Leu61Met) 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 pathogenic 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. L61F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CARTPT NM_004291.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.789
• Publications: 0 publications found

Genes affected

CARTPT (HGNC:24323): (CART prepropeptide) This gene encodes a preproprotein that is proteolytically processed to generate multiple biologically active peptides. These peptides play a role in appetite, energy balance, maintenance of body weight, reward and addiction, and the stress response. Expression of a similar gene transcript in rodents is upregulated following administration of cocaine and amphetamine. Mutations in this gene are associated with susceptibility to obesity in humans. [provided by RefSeq, Feb 2016]

CARTPT Gene-Disease associations (from GenCC):

• inherited obesity

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.909

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004291.4. 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
	CARTPT	NM_004291.4	MANE Select	c.181T>A	p.Leu61Met	missense	Exon 2 of 3	NP_004282.1	Q16568

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARTPT	ENST00000296777.5	TSL:1 MANE Select	c.181T>A	p.Leu61Met	missense	Exon 2 of 3	ENSP00000296777.4	Q16568
	CARTPT	ENST00000513096.1	TSL:2	n.323T>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.37	N
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.098	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.79
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Varity_R		0.77
gMVP		0.62
Mutation Taster		=73/27	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs930693952;

hg19: chr5-71015728;