22-43143114-G-C

Position:

chr22-43143114-G-C

Variant summary

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

The NM_173467.5(MCAT):c.235C>G(p.Arg79Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00466 in 1,602,372 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0048 ( 20 hom. )

Consequence

MCAT
NM_173467.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter U:1B:2

Conservation

PhyloP100: 1.32

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=0.0092794).

BP6

Variant 22-43143114-G-C is Benign according to our data. Variant chr22-43143114-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1695049.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MCAT	NM_173467.5 link	c.235C>G	p.Arg79Gly	missense_variant	1/4	ENST00000290429.11	NP_775738.3
MCAT	NM_014507.3 link	c.235C>G	p.Arg79Gly	missense_variant	1/3		NP_055322.1
MCAT	NR_046423.1 link	n.284C>G		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MCAT	ENST00000290429.11 link	c.235C>G	p.Arg79Gly	missense_variant	1/4	1	NM_173467.5	ENSP00000290429.5	Q8IVS2-1
MCAT	ENST00000327555.5 link	c.235C>G	p.Arg79Gly	missense_variant	1/3	1		ENSP00000331306.5	Q8IVS2-2
MCAT	ENST00000464244.1 link	n.167C>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00344

AC:

523

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00433

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00554

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00289

AC:

646

AN:

223410

Hom.:

AF XY:

0.00297

AC XY:

367

AN XY:

123658

show subpopulations

Gnomad AFR exome

AF:

0.000665

Gnomad AMR exome

AF:

0.00292

Gnomad ASJ exome

AF:

0.000105

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00148

Gnomad FIN exome

AF:

0.00385

Gnomad NFE exome

AF:

0.00413

Gnomad OTH exome

AF:

0.00480

GnomAD4 exome

AF:

0.00479

AC:

6941

AN:

1450006

Hom.:

Cov.:

AF XY:

0.00468

AC XY:

3374

AN XY:

721426

show subpopulations

Gnomad4 AFR exome

AF:

0.000990

Gnomad4 AMR exome

AF:

0.00319

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00168

Gnomad4 FIN exome

AF:

0.00343

Gnomad4 NFE exome

AF:

0.00563

Gnomad4 OTH exome

AF:

0.00356

GnomAD4 genome

AF:

0.00343

AC:

523

AN:

152366

Hom.:

Cov.:

AF XY:

0.00342

AC XY:

255

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000827

Gnomad4 FIN

AF:

0.00433

Gnomad4 NFE

AF:

0.00554

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00418

Hom.:

Bravo

AF:

0.00349

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00375

AC:

ExAC

AF:

0.00243

AC:

290

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Retinal dystrophy

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Jan 01, 2022

- -

MCAT-related condition

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 28, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

MCAT: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.48

T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.0093

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

2.0

M;M

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.3

D;D

REVEL

Benign

0.092

Sift

Benign

0.17

T;T

Sift4G

Uncertain

0.042

D;T

Polyphen

0.011

B;.

Vest4

0.31

MVP

0.59

MPC

0.39

ClinPred

0.041

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.54

gMVP

0.60

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