Variant 22-43133308-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_173467.5(MCAT):c.908C>G(p.Ala303Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 1,613,888 control chromosomes in the GnomAD database, including 341,375 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.55 ( 25273 hom., cov: 32)

Exomes 𝑓: 0.65 ( 316102 hom. )

Consequence

MCAT
NM_173467.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.05

Variant links:

Genes affected

MCAT (HGNC:29622): (malonyl-CoA-acyl carrier protein transacylase) The protein encoded by this gene is found exclusively in the mitochondrion, where it catalyzes the transfer of a malonyl group from malonyl-CoA to the mitochondrial acyl carrier protein. The encoded protein may be part of a fatty acid synthase complex that is more like the type II prokaryotic and plastid complexes rather than the type I human cytosolic complex. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2012]

MCAT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.712513E-6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MCAT	NM_173467.5 linkuse as main transcript	c.908C>G	p.Ala303Gly	missense_variant	4/4	ENST00000290429.11
MCAT	NM_014507.3 linkuse as main transcript	c.*147C>G		3_prime_UTR_variant	3/3
MCAT	NR_046423.1 linkuse as main transcript	n.773C>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCAT	ENST00000290429.11 linkuse as main transcript	c.908C>G	p.Ala303Gly	missense_variant	4/4	1	NM_173467.5	P1	Q8IVS2-1
MCAT	ENST00000327555.5 linkuse as main transcript	c.*147C>G		3_prime_UTR_variant	3/3	1			Q8IVS2-2

Frequencies

GnomAD3 genomes

AF:

0.548

AC:

83298

AN:

151916

Hom.:

25267

Cov.:

show subpopulations

Gnomad AFR

AF:

0.278

Gnomad AMI

AF:

0.814

Gnomad AMR

AF:

0.540

Gnomad ASJ

AF:

0.585

Gnomad EAS

AF:

0.610

Gnomad SAS

AF:

0.510

Gnomad FIN

AF:

0.712

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.681

Gnomad OTH

AF:

0.567

GnomAD3 exomes

AF:

0.606

AC:

152471

AN:

251488

Hom.:

47980

AF XY:

0.609

AC XY:

82797

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.266

Gnomad AMR exome

AF:

0.559

Gnomad ASJ exome

AF:

0.569

Gnomad EAS exome

AF:

0.599

Gnomad SAS exome

AF:

0.516

Gnomad FIN exome

AF:

0.697

Gnomad NFE exome

AF:

0.681

Gnomad OTH exome

AF:

0.613

GnomAD4 exome

AF:

0.652

AC:

953452

AN:

1461854

Hom.:

316102

Cov.:

AF XY:

0.650

AC XY:

472524

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.258

Gnomad4 AMR exome

AF:

0.555

Gnomad4 ASJ exome

AF:

0.571

Gnomad4 EAS exome

AF:

0.591

Gnomad4 SAS exome

AF:

0.528

Gnomad4 FIN exome

AF:

0.697

Gnomad4 NFE exome

AF:

0.682

Gnomad4 OTH exome

AF:

0.617

GnomAD4 genome

AF:

0.548

AC:

83347

AN:

152034

Hom.:

25273

Cov.:

AF XY:

0.546

AC XY:

40597

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.279

Gnomad4 AMR

AF:

0.539

Gnomad4 ASJ

AF:

0.585

Gnomad4 EAS

AF:

0.610

Gnomad4 SAS

AF:

0.511

Gnomad4 FIN

AF:

0.712

Gnomad4 NFE

AF:

0.681

Gnomad4 OTH

AF:

0.567

Alfa

AF:

0.647

Hom.:

22843

Bravo

AF:

0.528

TwinsUK

AF:

0.674

AC:

2500

ALSPAC

AF:

0.688

AC:

2653

ESP6500AA

AF:

0.291

AC:

1280

ESP6500EA

AF:

0.680

AC:

5845

ExAC

AF:

0.604

AC:

73380

Asia WGS

AF:

0.523

AC:

1815

AN:

3478

EpiCase

AF:

0.669

EpiControl

AF:

0.658

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.54

DEOGEN2

Benign

0.20

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0000067

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.36

MutationTaster

Benign

0.99

P;P

PrimateAI

Benign

0.39

PROVEAN

Benign

4.5

REVEL

Benign

0.18

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.028

MPC

0.30

ClinPred

0.0054

GERP RS

5.5

Varity_R

0.087

gMVP

0.67

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over