chr9-129095447-G-G

Variant names:

• chr9-129095447-G-G
• NM_000755.5:c.

Variant summary

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

The NM_000755.5(CRAT):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CRAT NM_000755.5 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.76
• 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 2 ACMG points.

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

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.		exon_region	Exon 14 of 14	NP_000746.3
	CRAT	NM_001346546.2		c.		exon_region	Exon 15 of 15	NP_001333475.2
	CRAT	NM_001257363.3		c.		exon_region	Exon 15 of 15	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.		exon_region	Exon 14 of 14	ENSP00000315013.2	P43155-1
	CRAT	ENST00000458362.5	TSL:1	n.		exon_region	Exon 15 of 15	ENSP00000400367.1	F2Z2C5
	CRAT	ENST00000458362.5	TSL:1	n.		3_prime_UTR	Exon 15 of 15	ENSP00000400367.1	F2Z2C5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.8

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: chr9-131857726;