Variant chr9-129095408-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000755.5(CRAT):c.1870G>C(p.Ala624Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0187 in 1,610,904 control chromosomes in the GnomAD database, including 1,181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.022 ( 111 hom., cov: 33)

Exomes 𝑓: 0.018 ( 1070 hom. )

Consequence

CRAT
NM_000755.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.76

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015979111).

BP6

Variant 9-129095408-C-G is Benign according to our data. Variant chr9-129095408-C-G is described in ClinVar as [Benign]. Clinvar id is 1167631.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRAT	NM_000755.5 linkuse as main transcript	c.1870G>C	p.Ala624Pro	missense_variant	14/14	ENST00000318080.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRAT	ENST00000318080.7 linkuse as main transcript	c.1870G>C	p.Ala624Pro	missense_variant	14/14	1	NM_000755.5	P1	P43155-1

Frequencies

GnomAD3 genomes

AF:

0.0219

AC:

3338

AN:

152142

Hom.:

111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.0351

Gnomad EAS

AF:

0.0702

Gnomad SAS

AF:

0.0439

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00855

Gnomad OTH

AF:

0.0234

GnomAD3 exomes

AF:

0.0423

AC:

10459

AN:

247244

Hom.:

749

AF XY:

0.0373

AC XY:

5014

AN XY:

134438

show subpopulations

Gnomad AFR exome

AF:

0.00840

Gnomad AMR exome

AF:

0.179

Gnomad ASJ exome

AF:

0.0409

Gnomad EAS exome

AF:

0.0759

Gnomad SAS exome

AF:

0.0398

Gnomad FIN exome

AF:

0.000543

Gnomad NFE exome

AF:

0.00861

Gnomad OTH exome

AF:

0.0319

GnomAD4 exome

AF:

0.0184

AC:

26771

AN:

1458644

Hom.:

1070

Cov.:

AF XY:

0.0182

AC XY:

13185

AN XY:

725712

show subpopulations

Gnomad4 AFR exome

AF:

0.00816

Gnomad4 AMR exome

AF:

0.168

Gnomad4 ASJ exome

AF:

0.0400

Gnomad4 EAS exome

AF:

0.0692

Gnomad4 SAS exome

AF:

0.0381

Gnomad4 FIN exome

AF:

0.000747

Gnomad4 NFE exome

AF:

0.00933

Gnomad4 OTH exome

AF:

0.0235

GnomAD4 genome

AF:

0.0220

AC:

3352

AN:

152260

Hom.:

111

Cov.:

AF XY:

0.0232

AC XY:

1727

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00967

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.0351

Gnomad4 EAS

AF:

0.0707

Gnomad4 SAS

AF:

0.0443

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00855

Gnomad4 OTH

AF:

0.0255

Alfa

AF:

0.0151

Hom.:

Bravo

AF:

0.0312

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.00885

AC:

ESP6500EA

AF:

0.00873

AC:

ExAC

AF:

0.0358

AC:

4345

Asia WGS

AF:

0.0680

AC:

237

AN:

3478

EpiCase

AF:

0.00949

EpiControl

AF:

0.00966

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Benign

0.016

Eigen_PC

Benign

0.083

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.37

Sift

Uncertain

0.010

Sift4G

Uncertain

0.028

Polyphen

0.014

Vest4

0.084

MPC

0.77

ClinPred

0.027

GERP RS

3.7

Varity_R

0.27

gMVP

0.76

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over