NM_000755.5:c.1844G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000755.5(CRAT):c.1844G>T(p.Arg615Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000688 in 1,612,816 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R615H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00036 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00072 ( 25 hom. )

Consequence

CRAT
NM_000755.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.66

Publications

4 publications found

Variant links:

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

CRAT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016620278).

BP6

Variant 9-129095434-C-A is Benign according to our data. Variant chr9-129095434-C-A is described in ClinVar as Benign. ClinVar VariationId is 1598787.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 25 Unknown,AR gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRAT	NM_000755.5	MANE Select	c.1844G>T	p.Arg615Leu	missense	Exon 14 of 14	NP_000746.3
CRAT	NM_001346546.2		c.1847G>T	p.Arg616Leu	missense	Exon 15 of 15	NP_001333475.2
CRAT	NM_001257363.3		c.1781G>T	p.Arg594Leu	missense	Exon 15 of 15	NP_001244292.2	P43155-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRAT	ENST00000318080.7	TSL:1 MANE Select	c.1844G>T	p.Arg615Leu	missense	Exon 14 of 14	ENSP00000315013.2	P43155-1
CRAT	ENST00000458362.5	TSL:1	n.*1820G>T		non_coding_transcript_exon	Exon 15 of 15	ENSP00000400367.1	F2Z2C5
CRAT	ENST00000458362.5	TSL:1	n.*1820G>T		3_prime_UTR	Exon 15 of 15	ENSP00000400367.1	F2Z2C5

Frequencies

GnomAD3 genomes

AF:

0.000368

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00931

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00133

AC:

333

AN:

249622

AF XY:

0.00196

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.0000999

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000240

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000722

AC:

1055

AN:

1460538

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

766

AN XY:

726610

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33476

American (AMR)

AF:

0.0000447

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0105

AC:

902

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52214

Middle Eastern (MID)

AF:

0.00246

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.0000755

AC:

AN:

1111986

Other (OTH)

AF:

0.000812

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

152

228

304

380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000361

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41568

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00911

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

67980

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000311

Hom.:

Bravo

AF:

0.0000982

ExAC

AF:

0.00144

AC:

175

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.65

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.20

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

MetaRNN

Benign

0.017

MetaSVM

Uncertain

0.091

MutationAssessor

Uncertain

2.2

PhyloP100

2.7

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-4.2

REVEL

Pathogenic

0.69

Sift

Benign

0.030

Sift4G

Benign

0.14

Polyphen

0.96

Vest4

0.64

MVP

0.94

MPC

0.87

ClinPred

0.13

GERP RS

3.7

Varity_R

0.76

gMVP

0.76

Mutation Taster

=83/17

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over