Variant 22-43133055-C-A 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_173467.5(MCAT):c.1161G>T(p.Glu387Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00408 in 1,613,410 control chromosomes in the GnomAD database, including 245 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.021 ( 117 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 128 hom. )

Consequence

MCAT
NM_173467.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00600

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019297302).

BP6

Variant 22-43133055-C-A is Benign according to our data. Variant chr22-43133055-C-A is described in ClinVar as [Benign]. Clinvar id is 784422.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MCAT	NM_173467.5 linkuse as main transcript	c.1161G>T	p.Glu387Asp	missense_variant	4/4	ENST00000290429.11
MCAT	NM_014507.3 linkuse as main transcript	c.*400G>T		3_prime_UTR_variant	3/3
MCAT	NR_046423.1 linkuse as main transcript	n.1026G>T		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.1161G>T	p.Glu387Asp	missense_variant	4/4	1	NM_173467.5	P1	Q8IVS2-1
MCAT	ENST00000327555.5 linkuse as main transcript	c.*400G>T		3_prime_UTR_variant	3/3	1			Q8IVS2-2

Frequencies

GnomAD3 genomes

AF:

0.0212

AC:

3224

AN:

152104

Hom.:

117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0743

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00674

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.00562

AC:

1412

AN:

251222

Hom.:

AF XY:

0.00379

AC XY:

514

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.0791

Gnomad AMR exome

AF:

0.00275

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00230

AC:

3362

AN:

1461188

Hom.:

128

Cov.:

AF XY:

0.00196

AC XY:

1424

AN XY:

726778

show subpopulations

Gnomad4 AFR exome

AF:

0.0813

Gnomad4 AMR exome

AF:

0.00295

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000194

Gnomad4 OTH exome

AF:

0.00417

GnomAD4 genome

AF:

0.0212

AC:

3226

AN:

152222

Hom.:

117

Cov.:

AF XY:

0.0201

AC XY:

1495

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0741

Gnomad4 AMR

AF:

0.00673

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.00360

Hom.:

Bravo

AF:

0.0239

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0704

AC:

310

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00697

AC:

846

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000296

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

Jun 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.65

Cadd

Benign

7.1

Dann

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.26

REVEL

Benign

0.018

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.067

Vest4

0.13

MutPred

0.22

Loss of glycosylation at P389 (P = 0.0872);

MVP

0.71

MPC

0.27

ClinPred

0.017

GERP RS

-1.8

Varity_R

0.061

gMVP

0.46

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