1-25489281-A-C
Position:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_018202.6(MACO1):āc.1605A>Cā(p.Glu535Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,613,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 32)
Exomes š: 0.000053 ( 0 hom. )
Consequence
MACO1
NM_018202.6 missense
NM_018202.6 missense
Scores
1
7
9
Clinical Significance
Conservation
PhyloP100: 0.0460
Genes affected
MACO1 (HGNC:25572): (macoilin 1) Predicted to enable actin filament binding activity and microtubule binding activity. Involved in neuronal signal transduction. Located in rough endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PP2
Missense variant where missense usually causes diseases, MACO1
BP4
Computational evidence support a benign effect (MetaRNN=0.39234287).
BS2
High AC in GnomAdExome4 at 77 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MACO1 | NM_018202.6 | c.1605A>C | p.Glu535Asp | missense_variant | 9/11 | ENST00000374343.5 | |
MACO1 | NM_001282564.2 | c.924A>C | p.Glu308Asp | missense_variant | 7/9 | ||
MACO1 | XM_005245931.3 | c.1605A>C | p.Glu535Asp | missense_variant | 9/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MACO1 | ENST00000374343.5 | c.1605A>C | p.Glu535Asp | missense_variant | 9/11 | 1 | NM_018202.6 | P1 | |
MACO1 | ENST00000399766.7 | c.924A>C | p.Glu308Asp | missense_variant | 7/9 | 1 | |||
MACO1 | ENST00000647928.1 | c.*433A>C | 3_prime_UTR_variant, NMD_transcript_variant | 9/11 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152224Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
4
AN:
152224
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250848Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135664
GnomAD3 exomes
AF:
AC:
2
AN:
250848
Hom.:
AF XY:
AC XY:
0
AN XY:
135664
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000527 AC: 77AN: 1461552Hom.: 0 Cov.: 30 AF XY: 0.0000509 AC XY: 37AN XY: 727086
GnomAD4 exome
AF:
AC:
77
AN:
1461552
Hom.:
Cov.:
30
AF XY:
AC XY:
37
AN XY:
727086
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74386
GnomAD4 genome
AF:
AC:
4
AN:
152224
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74386
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
1
ALSPAC
AF:
AC:
0
ExAC
AF:
AC:
1
EpiCase
AF:
EpiControl
AF:
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 11, 2023 | The c.1605A>C (p.E535D) alteration is located in exon 9 (coding exon 9) of the TMEM57 gene. This alteration results from a A to C substitution at nucleotide position 1605, causing the glutamic acid (E) at amino acid position 535 to be replaced by an aspartic acid (D). 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
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Uncertain
D;T
Sift4G
Benign
T;T
Polyphen
P;D
Vest4
MutPred
0.57
.;Gain of MoRF binding (P = 0.0939);
MVP
MPC
2.0
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at