Variant 14-39247105-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000640607.2(MIA2):c.531A>C(p.Gln177His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,456,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

MIA2
ENST00000640607.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.123

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=0.13853022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIA2	NM_001329214.4 linkuse as main transcript	c.531A>C	p.Gln177His	missense_variant	4/29	ENST00000640607.2	NP_001316143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIA2	ENST00000640607.2 linkuse as main transcript	c.531A>C	p.Gln177His	missense_variant	4/29	1	NM_001329214.4	ENSP00000491014	P2	Q96PC5-3
MIA2	ENST00000280082.4 linkuse as main transcript	c.531A>C	p.Gln177His	missense_variant	4/6	1		ENSP00000280082		Q96PC5-2
MIA2	ENST00000553728.1 linkuse as main transcript	c.531A>C	p.Gln177His	missense_variant	4/28	5		ENSP00000452252	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000410

AC:

AN:

244090

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131698

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000895

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1456084

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

724040

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:

0.0000162

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Jan 23, 2023

The c.531A>C (p.Q177H) alteration is located in exon 4 (coding exon 4) of the MIA2 gene. This alteration results from a A to C substitution at nucleotide position 531, causing the glutamine (Q) at amino acid position 177 to be replaced by a histidine (H). 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

0.12

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

7.8

DANN

Uncertain

0.99

DEOGEN2

Benign

0.044

.;.;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.3

.;M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.88

N;N;.

REVEL

Benign

0.10

Sift

Uncertain

0.014

D;D;.

Sift4G

Benign

0.33

T;D;.

Polyphen

1.0

.;D;D

Vest4

0.26

MutPred

0.31

Gain of catalytic residue at D176 (P = 0.0377);Gain of catalytic residue at D176 (P = 0.0377);Gain of catalytic residue at D176 (P = 0.0377);

MVP

0.59

MPC

0.18

ClinPred

0.59

GERP RS

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.042

gMVP

0.22

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