22-43143114-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.32

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]

ACMG classification

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 GnomAdExome at 2 AR gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCAT	ENST00000290429.11	c.235C>G	p.Arg79Gly	missense_variant	1/4	1	NM_173467.5	P1
MCAT	ENST00000327555.5	c.235C>G	p.Arg79Gly	missense_variant	1/3	1
MCAT	ENST00000464244.1	n.167C>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.00344 AC: 523 AN: 152248 Hom.: 0 Cov.: 33

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.: 2 AF XY: 0.00297 AC XY: 367 AN XY: 123658

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.: 20 Cov.: 32 AF XY: 0.00468 AC XY: 3374 AN XY: 721426

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.: 0 Cov.: 33 AF XY: 0.00342 AC XY: 255 AN XY: 74510

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.: 0

Bravo AF: 0.00349

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.00375 AC: 32

ExAC AF: 0.00243 AC: 290

Asia WGS AF: 0.000866 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	22
Dann	Uncertain	0.98
DEOGEN2	Uncertain	0.48	T;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.0093	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	2.0	M;M
MutationTaster	Benign	0.98	D;D
PrimateAI	Uncertain	0.69	T
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	T
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

Other links and lift over

dbSNP: rs77536207; hg19: chr22-43539120;