9-129095433-AC-TA

Variant names:

• chr9-129095433-AC-TA
• NM_000755.5:c.1844_1845delGTinsTA
• CRAT p.Arg615Leu

Variant summary

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

The NM_000755.5(CRAT):​c.1844_1845delGTinsTA​(p.Arg615Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R615C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CRAT NM_000755.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.66
• Publications: 0 publications found

Genes affected

CRAT (HGNC:2342): (carnitine O-acetyltransferase) This gene encodes carnitine O-acetyltransferase, a member of the carnitine acyltransferase family and a key metabolic pathway enzyme which plays an important role in energy homeostasis and fat metabolism. This enzyme catalyzes the reversible transfer of acyl groups from an acyl-CoA thioester to carnitine and regulates the ratio of acyl-CoA/CoA. It is found in both the mitochondria and the peroxisome. Alternative splicing results in transcript variants encoding different isoforms that may localize to different subcellular compartments. [provided by RefSeq, Oct 2016]

CRAT Gene-Disease associations (from GenCC):

• neurodegeneration with brain iron accumulation 8

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000755.5. 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
	CRAT	NM_000755.5	MANE Select	c.1844_1845delGTinsTA	p.Arg615Leu	missense	N/A	NP_000746.3
	CRAT	NM_001346546.2		c.1847_1848delGTinsTA	p.Arg616Leu	missense	N/A	NP_001333475.2
	CRAT	NM_001257363.3		c.1781_1782delGTinsTA	p.Arg594Leu	missense	N/A	NP_001244292.2	P43155-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRAT	ENST00000318080.7	TSL:1 MANE Select	c.1844_1845delGTinsTA	p.Arg615Leu	missense	N/A	ENSP00000315013.2	P43155-1
	CRAT	ENST00000458362.5	TSL:1	n.*1820_*1821delGTinsTA		non_coding_transcript_exon	Exon 15 of 15	ENSP00000400367.1	F2Z2C5
	CRAT	ENST00000458362.5	TSL:1	n.*1820_*1821delGTinsTA		3_prime_UTR	Exon 15 of 15	ENSP00000400367.1	F2Z2C5

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

Splicing

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

hg19: chr9-131857712;