chr22-43143060-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_173467.5(MCAT):c.289G>T(p.Val97Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000404 in 1,609,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
MCAT
NM_173467.5 missense
NM_173467.5 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 3.58
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.11098641).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MCAT | NM_173467.5 | c.289G>T | p.Val97Leu | missense_variant | 1/4 | ENST00000290429.11 | |
MCAT | NM_014507.3 | c.289G>T | p.Val97Leu | missense_variant | 1/3 | ||
MCAT | NR_046423.1 | n.338G>T | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCAT | ENST00000290429.11 | c.289G>T | p.Val97Leu | missense_variant | 1/4 | 1 | NM_173467.5 | P1 | |
MCAT | ENST00000327555.5 | c.289G>T | p.Val97Leu | missense_variant | 1/3 | 1 | |||
MCAT | ENST00000464244.1 | n.221G>T | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152226Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000807 AC: 19AN: 235582Hom.: 0 AF XY: 0.0000618 AC XY: 8AN XY: 129538
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GnomAD4 exome AF: 0.0000254 AC: 37AN: 1457518Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 725102
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GnomAD4 genome ? AF: 0.000184 AC: 28AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74358
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 10, 2023 | The c.289G>T (p.V97L) alteration is located in exon 1 (coding exon 1) of the MCAT gene. This alteration results from a G to T substitution at nucleotide position 289, causing the valine (V) at amino acid position 97 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
D;D
Sift4G
Uncertain
D;T
Polyphen
B;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0941);Loss of MoRF binding (P = 0.0941);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at