Genetic Variant MCAT:c.*256A>G (chr22-43132787-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_173467.5(MCAT):c.*256A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 493,902 control chromosomes in the GnomAD database, including 94,426 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.51 ( 24066 hom., cov: 33)

Exomes 𝑓: 0.63 ( 70360 hom. )

Consequence

MCAT
NM_173467.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.82

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive optic atrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MCAT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
MCAT	NM_173467.5 link	c.*256A>G	3_prime_UTR_variant	Exon 4 of 4	ENST00000290429.11	NP_775738.3
MCAT	NR_046423.1 link	n.1294A>G	non_coding_transcript_exon_variant	Exon 3 of 3
MCAT	NM_014507.3 link	c.*668A>G	3_prime_UTR_variant	Exon 3 of 3		NP_055322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCAT	ENST00000290429.11 link	c.*256A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_173467.5	ENSP00000290429.5		Q8IVS2-1
MCAT	ENST00000327555.5 link	c.*668A>G		downstream_gene_variant		1		ENSP00000331306.5		Q8IVS2-2

Frequencies

GnomAD3 genomes

AF:

0.512

AC:

77895

AN:

152062

Hom.:

24066

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.814

Gnomad AMR

AF:

0.529

Gnomad ASJ

AF:

0.585

Gnomad EAS

AF:

0.612

Gnomad SAS

AF:

0.510

Gnomad FIN

AF:

0.712

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.681

Gnomad OTH

AF:

0.544

GnomAD4 exome

AF:

0.630

AC:

215185

AN:

341722

Hom.:

70360

Cov.:

AF XY:

0.626

AC XY:

112038

AN XY:

179004

show subpopulations

African (AFR)

AF:

0.150

AC:

1567

AN:

10470

American (AMR)

AF:

0.545

AC:

7802

AN:

14316

Ashkenazi Jewish (ASJ)

AF:

0.575

AC:

6164

AN:

10722

East Asian (EAS)

AF:

0.587

AC:

13288

AN:

22640

South Asian (SAS)

AF:

0.527

AC:

19632

AN:

37274

European-Finnish (FIN)

AF:

0.700

AC:

14378

AN:

20544

Middle Eastern (MID)

AF:

0.572

AC:

848

AN:

1482

European-Non Finnish (NFE)

AF:

0.683

AC:

139488

AN:

204364

Other (OTH)

AF:

0.604

AC:

12018

AN:

19910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

3548

7097

10645

14194

17742

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

606

1212

1818

2424

3030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.512

AC:

77910

AN:

152180

Hom.:

24066

Cov.:

AF XY:

0.511

AC XY:

38045

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.151

AC:

6273

AN:

41534

American (AMR)

AF:

0.529

AC:

8082

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.585

AC:

2030

AN:

3472

East Asian (EAS)

AF:

0.613

AC:

3162

AN:

5162

South Asian (SAS)

AF:

0.512

AC:

2470

AN:

4828

European-Finnish (FIN)

AF:

0.712

AC:

7549

AN:

10602

Middle Eastern (MID)

AF:

0.503

AC:

148

AN:

294

European-Non Finnish (NFE)

AF:

0.681

AC:

46305

AN:

67980

Other (OTH)

AF:

0.545

AC:

1149

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1594

3189

4783

6378

7972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

660

1320

1980

2640

3300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.629

Hom.:

26210

Bravo

AF:

0.488

Asia WGS

AF:

0.509

AC:

1768

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.69

(source)

DANN

Benign

0.48

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over