dbSNP rs36060072: MIA2:p.Pro1129Ala (chr14-39320945-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001329214.4(MIA2):c.3385C>G(p.Pro1129Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00583 in 1,613,264 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 37 hom. )

Consequence

MIA2
NM_001329214.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.51

Publications

16 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0094510615).

BP6

Variant 14-39320945-C-G is Benign according to our data. Variant chr14-39320945-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2644195.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIA2	NM_001329214.4 link	c.3385C>G	p.Pro1129Ala	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>G	p.Pro1129Ala	missense_variant	Exon 24 of 29	1	NM_001329214.4	ENSP00000491014.1		Q96PC5-3

Frequencies

GnomAD3 genomes

AF:

0.00436

AC:

663

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00537

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00667

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00470

AC:

1178

AN:

250682

AF XY:

0.00463

show subpopulations

Gnomad AFR exome

AF:

0.000985

Gnomad AMR exome

AF:

0.00241

Gnomad ASJ exome

AF:

0.00726

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00846

Gnomad NFE exome

AF:

0.00695

Gnomad OTH exome

AF:

0.00573

GnomAD4 exome

AF:

0.00598

AC:

8743

AN:

1460990

Hom.:

Cov.:

AF XY:

0.00582

AC XY:

4227

AN XY:

726810

show subpopulations

African (AFR)

AF:

0.00114

AC:

AN:

33420

American (AMR)

AF:

0.00278

AC:

124

AN:

44586

Ashkenazi Jewish (ASJ)

AF:

0.00781

AC:

204

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86188

European-Finnish (FIN)

AF:

0.00858

AC:

458

AN:

53394

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00684

AC:

7606

AN:

1111532

Other (OTH)

AF:

0.00512

AC:

309

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

424

848

1273

1697

2121

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

288

576

864

1152

1440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00435

AC:

663

AN:

152274

Hom.:

Cov.:

AF XY:

0.00404

AC XY:

301

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00113

AC:

AN:

41548

American (AMR)

AF:

0.00307

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00778

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00537

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00667

AC:

454

AN:

68024

Other (OTH)

AF:

0.00568

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

115

153

191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00567

Hom.:

Bravo

AF:

0.00411

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00686

AC:

ExAC

AF:

0.00476

AC:

578

EpiCase

AF:

0.00633

EpiControl

AF:

0.00723

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MIA2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

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

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.81

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

M_CAP

Benign

0.039

MetaRNN

Benign

0.0095

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

MetaSVM

Uncertain

-0.25

PhyloP100

3.5

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-4.7

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

REVEL

Uncertain

0.31

Sift

Uncertain

0.0050

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

Sift4G

Uncertain

0.043

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

Vest4

0.47

MVP

0.86

MPC

0.019

ClinPred

0.057

GERP RS

5.1

Varity_R

0.12

gMVP

0.43

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over