NM_000755.5:c.1830G>C

Variant names:

• chr9-129095448-C-G
• rs1012240026
• NM_000755.5:c.1830G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP6_Moderate BP7

The NM_000755.5(CRAT):​c.1830G>C​(p.Ala610Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CRAT NM_000755.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 9-129095448-C-G is Benign according to our data. Variant chr9-129095448-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2013431.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.76 with no splicing effect.

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.1830G>C	p.Ala610Ala	synonymous	Exon 14 of 14	NP_000746.3
	CRAT	NM_001346546.2		c.1833G>C	p.Ala611Ala	synonymous	Exon 15 of 15	NP_001333475.2
	CRAT	NM_001257363.3		c.1767G>C	p.Ala589Ala	synonymous	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.1830G>C	p.Ala610Ala	synonymous	Exon 14 of 14	ENSP00000315013.2	P43155-1
	CRAT	ENST00000458362.5	TSL:1	n.*1806G>C		non_coding_transcript_exon	Exon 15 of 15	ENSP00000400367.1	F2Z2C5
	CRAT	ENST00000458362.5	TSL:1	n.*1806G>C		3_prime_UTR	Exon 15 of 15	ENSP00000400367.1	F2Z2C5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.26
DANN	Benign	0.77
PhyloP100		-3.8
Mutation Taster		=100/0	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: rs1012240026; hg19: chr9-131857727;