rs36060072

chr14-39320945-C-Gchr14-39320945-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.51

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 2644195.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIA2	NM_001329214.4	c.3385C>G	p.Pro1129Ala	missense_variant	24/29	ENST00000640607.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIA2	ENST00000640607.2	c.3385C>G	p.Pro1129Ala	missense_variant	24/29	1	NM_001329214.4	P2

Frequencies

GnomAD3 genomes AF: 0.00436 AC: 663 AN: 152156 Hom.: 2 Cov.: 32

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

GnomAD3 exomes AF: 0.00470 AC: 1178 AN: 250682 Hom.: 6 AF XY: 0.00463 AC XY: 627 AN XY: 135490

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 SAS exome AF: 0.0000327

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.: 37 Cov.: 30 AF XY: 0.00582 AC XY: 4227 AN XY: 726810

Gnomad4 AFR exome AF: 0.00114

Gnomad4 AMR exome AF: 0.00278

Gnomad4 ASJ exome AF: 0.00781

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00858

Gnomad4 NFE exome AF: 0.00684

Gnomad4 OTH exome AF: 0.00512

GnomAD4 genome AF: 0.00435 AC: 663 AN: 152274 Hom.: 2 Cov.: 32 AF XY: 0.00404 AC XY: 301 AN XY: 74452

Gnomad4 AFR AF: 0.00113

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00537

Gnomad4 NFE AF: 0.00667

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00567 Hom.: 3

Bravo AF: 0.00411

TwinsUK AF: 0.00566 AC: 21

ALSPAC AF: 0.00727 AC: 28

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00686 AC: 59

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

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

MIA2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.28
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T;T;T;T;.;T;T;T;T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.0095	T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.25	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.56	T
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	T
GERP RS		5.1
Varity_R		0.12
gMVP		0.43

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

Other links and lift over

dbSNP: rs36060072; hg19: chr14-39790149; COSMIC: COSV99039607;