22-43132787-T-A

Variant names:

• chr22-43132787-T-A
• rs737802
• NM_173467.5:c.*256A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173467.5(MCAT):​c.*256A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MCAT NM_173467.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 7 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCAT	NM_173467.5	c.*256A>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000290429.11	NP_775738.3
MCAT	NR_046423.1	n.1294A>T		non_coding_transcript_exon_variant	Exon 3 of 3
MCAT	NM_014507.3	c.*668A>T		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	c.*256A>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_173467.5	ENSP00000290429.5
MCAT	ENST00000327555.5	c.*668A>T		downstream_gene_variant		1		ENSP00000331306.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 342596 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 179458

African (AFR) AF: 0.00 AC: 0 AN: 10470

American (AMR) AF: 0.00 AC: 0 AN: 14362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10760

East Asian (EAS) AF: 0.00 AC: 0 AN: 22706

South Asian (SAS) AF: 0.00 AC: 0 AN: 37346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1488

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 204876

Other (OTH) AF: 0.00 AC: 0 AN: 19978

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 26210

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.55
DANN	Benign	0.74
PhyloP100		-1.8

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

Other links and lift over

dbSNP: rs737802; hg19: chr22-43528793;