Variant 22-43133088-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_173467.5(MCAT):c.1128G>C(p.Gln376His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000845 in 1,614,190 control chromosomes in the GnomAD database, including 12 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 0.0046 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00046 ( 3 hom. )

Consequence

MCAT
NM_173467.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.633

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003996372).

BP6

Variant 22-43133088-C-G is Benign according to our data. Variant chr22-43133088-C-G is described in ClinVar as [Benign]. Clinvar id is 716517.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MCAT	NM_173467.5 linkuse as main transcript	c.1128G>C	p.Gln376His	missense_variant	4/4	ENST00000290429.11
MCAT	NM_014507.3 linkuse as main transcript	c.*367G>C		3_prime_UTR_variant	3/3
MCAT	NR_046423.1 linkuse as main transcript	n.993G>C		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.1128G>C	p.Gln376His	missense_variant	4/4	1	NM_173467.5	P1	Q8IVS2-1
MCAT	ENST00000327555.5 linkuse as main transcript	c.*367G>C		3_prime_UTR_variant	3/3	1			Q8IVS2-2

Frequencies

GnomAD3 genomes

AF:

0.00458

AC:

697

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0160

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00122

AC:

307

AN:

251484

Hom.:

AF XY:

0.000876

AC XY:

119

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0170

Gnomad AMR exome

AF:

0.000723

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:

0.0000264

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000457

AC:

668

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000391

AC XY:

284

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0155

Gnomad4 AMR exome

AF:

0.000939

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000414

Gnomad4 OTH exome

AF:

0.000861

GnomAD4 genome

AF:

0.00457

AC:

696

AN:

152314

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

313

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0160

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000380

Hom.:

Bravo

AF:

0.00522

ESP6500AA

AF:

0.0148

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00145

AC:

176

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Feb 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.69

Cadd

Benign

9.5

Dann

Uncertain

0.99

DEOGEN2

Benign

0.26

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0040

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.88

REVEL

Benign

0.11

Sift

Uncertain

0.010

Sift4G

Uncertain

0.014

Polyphen

0.73

Vest4

0.060

MutPred

0.65

Loss of solvent accessibility (P = 0.0635);

MVP

0.73

MPC

0.78

ClinPred

0.022

GERP RS

4.3

Varity_R

0.044

gMVP

0.35

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