Variant 1-25431138-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4

The NM_018202.6(MACO1):c.40C>A(p.Pro14Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000375 in 1,598,718 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 (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MACO1
NM_018202.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.67

Variant links:

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]

MACO1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP2

Missense variant where missense usually causes diseases, MACO1

BP4

Computational evidence support a benign effect (MetaRNN=0.3789728).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MACO1	NM_018202.6 linkuse as main transcript	c.40C>A	p.Pro14Thr	missense_variant	1/11	ENST00000374343.5
MACO1	NM_001282564.2 linkuse as main transcript	c.40C>A	p.Pro14Thr	missense_variant	1/9
MACO1	XM_005245931.3 linkuse as main transcript	c.40C>A	p.Pro14Thr	missense_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACO1	ENST00000374343.5 linkuse as main transcript	c.40C>A	p.Pro14Thr	missense_variant	1/11	1	NM_018202.6	P1	Q8N5G2-1
MACO1	ENST00000399766.7 linkuse as main transcript	c.40C>A	p.Pro14Thr	missense_variant	1/9	1			Q8N5G2-3
MACO1	ENST00000647928.1 linkuse as main transcript	c.40C>A	p.Pro14Thr	missense_variant, NMD_transcript_variant	1/11

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1446658

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719528

show subpopulations

Gnomad4 AFR exome

AF:

0.0000319

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Dec 22, 2023

The c.40C>A (p.P14T) alteration is located in exon 1 (coding exon 1) of the TMEM57 gene. This alteration results from a C to A substitution at nucleotide position 40, causing the proline (P) at amino acid position 14 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Benign

-0.20

Cadd

Uncertain

Dann

Benign

0.97

Eigen

Benign

0.061

Eigen_PC

Benign

0.098

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.96

D;D

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.38

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

2.0

M;M

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-6.1

D;D

REVEL

Uncertain

0.29

Sift

Uncertain

0.021

D;D

Sift4G

Uncertain

0.012

D;D

Polyphen

0.21

B;B

Vest4

0.23

MutPred

0.56

Loss of loop (P = 0.0031);Loss of loop (P = 0.0031);

MVP

0.10

MPC

1.8

ClinPred

0.97

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.84

gMVP

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over