Genetic Variant MIA2:p.Pro1129Ser (chr14-39320945-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001329214.4(MIA2):c.3385C>T(p.Pro1129Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,613,386 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 1 hom. )

Consequence

MIA2
NM_001329214.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.51

Variant links:

Genes affected

MIA2 (HGNC:18432): (MIA SH3 domain ER export factor 2) This gene encodes s receptor in the endoplasmic reticulum, which plays a role in the export of large pre-chylomicrons and pre-very low density lipoproteins (pre-VLDLs). Three major classes of transcripts are generated from this gene- melanoma inhibitory activity 2-specific transcripts, cTAGE family member 5-specific transcripts and transcripts that include exons from both these transcript species (TANGO1-like or TALI). Additionally, alternative splicing in these transcripts results in multiple transcript variants encoding multiple isoforms. [provided by RefSeq, Sep 2016]

MIA2 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=0.22739616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIA2	NM_001329214.4 link	c.3385C>T	p.Pro1129Ser	missense_variant	Exon 24 of 29	ENST00000640607.2	NP_001316143.1	Q96PC5-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIA2	ENST00000640607.2 link	c.3385C>T	p.Pro1129Ser	missense_variant	Exon 24 of 29	1	NM_001329214.4	ENSP00000491014.1		Q96PC5-3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000598

AC:

AN:

250682

Hom.:

AF XY:

0.0000738

AC XY:

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000458

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1461108

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

726864

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:

0.000545

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000741

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

.;D;.;.;.;.;.;.;.;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.74

T;T;T;T;.;T;T;T;T;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.23

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.40

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-4.7

D;.;D;D;D;D;D;D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.021

D;.;D;D;D;D;D;D;D;D

Sift4G

Benign

0.14

T;.;T;T;T;T;T;T;T;T

Vest4

0.58

MutPred

0.41

.;.;.;.;.;.;Gain of phosphorylation at P521 (P = 0.0243);Gain of phosphorylation at P521 (P = 0.0243);.;.;

MVP

0.84

MPC

0.024

ClinPred

0.39

GERP RS

5.1

Varity_R

0.12

gMVP

0.53

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over