Variant 2-27025723-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012326.4(MAPRE3):c.610G>A(p.Glu204Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MAPRE3
NM_012326.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.84

Variant links:

Genes affected

MAPRE3 (HGNC:6892): (microtubule associated protein RP/EB family member 3) The protein encoded by this gene is a member of the RP/EB family of genes. The protein localizes to the cytoplasmic microtubule network and binds APCL, a homolog of the adenomatous polyposis coli tumor suppressor gene. [provided by RefSeq, Jul 2008]

MAPRE3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPRE3	NM_012326.4 linkuse as main transcript	c.610G>A	p.Glu204Lys	missense_variant	5/7	ENST00000233121.7	NP_036458.2	Q9UPY8-1
MAPRE3	NM_001303050.2 linkuse as main transcript	c.610G>A	p.Glu204Lys	missense_variant	5/7		NP_001289979.1	Q9UPY8-1
MAPRE3	NM_001410716.1 linkuse as main transcript	c.565G>A	p.Glu189Lys	missense_variant	5/7		NP_001397645.1
MAPRE3	XM_047443728.1 linkuse as main transcript	c.610G>A	p.Glu204Lys	missense_variant	5/7		XP_047299684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPRE3	ENST00000233121.7 linkuse as main transcript	c.610G>A	p.Glu204Lys	missense_variant	5/7	1	NM_012326.4	ENSP00000233121.2		Q9UPY8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727236

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000378

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

Sep 06, 2022

The c.610G>A (p.E204K) alteration is located in exon 5 (coding exon 4) of the MAPRE3 gene. This alteration results from a G to A substitution at nucleotide position 610, causing the glutamic acid (E) at amino acid position 204 to be replaced by a lysine (K). 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

0.66

BayesDel_addAF

Uncertain

0.028

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

T;.;.;T;.

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;.;.;D;D

M_CAP

Benign

0.054

MetaRNN

Uncertain

0.49

T;T;T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.2

M;.;.;.;.

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-2.6

D;D;.;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0050

D;D;.;D;D

Sift4G

Uncertain

0.042

D;T;.;T;T

Polyphen

0.84

P;P;P;.;P

Vest4

0.82

MutPred

0.47

Gain of ubiquitination at E204 (P = 0.0192);.;.;Gain of ubiquitination at E204 (P = 0.0192);.;

MVP

0.59

MPC

1.1

ClinPred

0.98

GERP RS

5.0

Varity_R

0.80

gMVP

0.90

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