Variant 2-27025616-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012326.4(MAPRE3):c.503A>T(p.Asn168Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,442,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MAPRE3
NM_012326.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.11

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.123741955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPRE3	NM_012326.4 linkuse as main transcript	c.503A>T	p.Asn168Ile	missense_variant	5/7	ENST00000233121.7	NP_036458.2	Q9UPY8-1
MAPRE3	NM_001303050.2 linkuse as main transcript	c.503A>T	p.Asn168Ile	missense_variant	5/7		NP_001289979.1	Q9UPY8-1
MAPRE3	NM_001410716.1 linkuse as main transcript	c.458A>T	p.Asn153Ile	missense_variant	5/7		NP_001397645.1
MAPRE3	XM_047443728.1 linkuse as main transcript	c.503A>T	p.Asn168Ile	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.503A>T	p.Asn168Ile	missense_variant	5/7	1	NM_012326.4	ENSP00000233121.2		Q9UPY8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1442624

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

716134

show subpopulations

Gnomad4 AFR exome

AF:

0.0000604

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:

0.0000168

GnomAD4 genome

Cov.:

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

Nov 20, 2024

The c.503A>T (p.N168I) alteration is located in exon 5 (coding exon 4) of the MAPRE3 gene. This alteration results from a A to T substitution at nucleotide position 503, causing the asparagine (N) at amino acid position 168 to be replaced by an isoleucine (I). 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

Benign

0.080

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.056

T;.;.;T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.84

T;.;.;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.;.;.;.

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.7

N;N;.;N;N

REVEL

Benign

0.061

Sift

Benign

0.25

T;T;.;T;T

Sift4G

Benign

0.19

T;T;.;T;T

Polyphen

0.53

P;B;B;.;B

Vest4

0.48

MutPred

0.14

Gain of methylation at K167 (P = 0.0455);.;.;Gain of methylation at K167 (P = 0.0455);.;

MVP

0.47

MPC

1.1

ClinPred

0.42

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.77

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