Variant 1-25448835-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018202.6(MACO1):c.250G>A(p.Ala84Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MACO1
NM_018202.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.52

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.893

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACO1	NM_018202.6 linkuse as main transcript	c.250G>A	p.Ala84Thr	missense_variant	3/11	ENST00000374343.5	NP_060672.2	Q8N5G2-1
MACO1	NM_001282564.2 linkuse as main transcript	c.250G>A	p.Ala84Thr	missense_variant	3/9		NP_001269493.1	Q8N5G2-3
MACO1	XM_005245931.3 linkuse as main transcript	c.250G>A	p.Ala84Thr	missense_variant	3/10		XP_005245988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MACO1	ENST00000374343.5 linkuse as main transcript	c.250G>A	p.Ala84Thr	missense_variant	3/11	1	NM_018202.6	ENSP00000363463.4	Q8N5G2-1
MACO1	ENST00000399766.7 linkuse as main transcript	c.250G>A	p.Ala84Thr	missense_variant	3/9	1		ENSP00000382668.3	Q8N5G2-3
MACO1	ENST00000647928.1 linkuse as main transcript	n.250G>A		non_coding_transcript_exon_variant	3/11			ENSP00000497738.1	A0A3B3ITD2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1404568

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

693540

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 16, 2023

The c.250G>A (p.A84T) alteration is located in exon 3 (coding exon 3) of the TMEM57 gene. This alteration results from a G to A substitution at nucleotide position 250, causing the alanine (A) at amino acid position 84 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

0.69

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

.;T

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D

M_CAP

Uncertain

0.091

MetaRNN

Pathogenic

0.89

D;D

MetaSVM

Uncertain

0.20

MutationAssessor

Benign

2.0

M;M

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-3.5

D;D

REVEL

Pathogenic

0.72

Sift

Benign

0.48

T;D

Sift4G

Benign

0.081

T;D

Polyphen

1.0

D;B

Vest4

0.73

MutPred

0.83

Gain of glycosylation at A84 (P = 0.0316);Gain of glycosylation at A84 (P = 0.0316);

MVP

0.72

MPC

1.4

ClinPred

0.98

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.72

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over