chr22-43132787-T-C

Position:

• chr22-43132787-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

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 -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	HGVSp	Effect	#exon/exons	MANE	UniProt
MCAT	NM_173467.5	c.*256A>G		3_prime_UTR_variant	4/4	ENST00000290429.11
MCAT	NM_014507.3	c.*668A>G		3_prime_UTR_variant	3/3
MCAT	NR_046423.1	n.1294A>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCAT	ENST00000290429.11	c.*256A>G		3_prime_UTR_variant	4/4	1	NM_173467.5	P1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77895 AN: 152062 Hom.: 24066 Cov.: 33

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.: 3 AF XY: 0.626 AC XY: 112038 AN XY: 179004

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.545

Gnomad4 ASJ exome AF: 0.575

Gnomad4 EAS exome AF: 0.587

Gnomad4 SAS exome AF: 0.527

Gnomad4 FIN exome AF: 0.700

Gnomad4 NFE exome AF: 0.683

Gnomad4 OTH exome AF: 0.604

GnomAD4 genome AF: 0.512 AC: 77910 AN: 152180 Hom.: 24066 Cov.: 33 AF XY: 0.511 AC XY: 38045 AN XY: 74406

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.613

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.545

Alfa AF: 0.623 Hom.: 12837

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
DANN	Benign	0.48

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: rs737802; hg19: chr22-43528793;