1-222627579-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001324064.2(MIA3):​c.-134C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00367 in 1,570,160 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0038 ( 17 hom. )

Consequence

MIA3
NM_001324064.2 5_prime_UTR_premature_start_codon_gain

Scores

3
9
6

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.09
Variant links:
Genes affected
MIA3 (HGNC:24008): (MIA SH3 domain ER export factor 3) Enables cargo receptor activity. Involved in several processes, including COPII-coated vesicle cargo loading; cell migration involved in sprouting angiogenesis; and regulation of leukocyte migration. Located in endoplasmic reticulum exit site and endoplasmic reticulum membrane. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.017081648).
BP6
Variant 1-222627579-C-T is Benign according to our data. Variant chr1-222627579-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3387972.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/exons MANE Protein UniProt
MIA3NM_198551.4 linkuse as main transcriptc.359C>T p.Thr120Met missense_variant 4/28 ENST00000344922.10 NP_940953.2 Q5JRA6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MIA3ENST00000344922.10 linkuse as main transcriptc.359C>T p.Thr120Met missense_variant 4/285 NM_198551.4 ENSP00000340900.5 Q5JRA6-1
MIA3ENST00000470521.1 linkuse as main transcriptn.371C>T non_coding_transcript_exon_variant 4/75

Frequencies

GnomAD3 genomes
AF:
0.00268
AC:
407
AN:
152016
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000653
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.00721
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00294
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00451
Gnomad OTH
AF:
0.00336
GnomAD3 exomes
AF:
0.00351
AC:
746
AN:
212718
Hom.:
2
AF XY:
0.00369
AC XY:
429
AN XY:
116112
show subpopulations
Gnomad AFR exome
AF:
0.000813
Gnomad AMR exome
AF:
0.000652
Gnomad ASJ exome
AF:
0.00749
Gnomad EAS exome
AF:
0.0000634
Gnomad SAS exome
AF:
0.000128
Gnomad FIN exome
AF:
0.00364
Gnomad NFE exome
AF:
0.00551
Gnomad OTH exome
AF:
0.00491
GnomAD4 exome
AF:
0.00377
AC:
5351
AN:
1418026
Hom.:
17
Cov.:
30
AF XY:
0.00377
AC XY:
2654
AN XY:
703602
show subpopulations
Gnomad4 AFR exome
AF:
0.000938
Gnomad4 AMR exome
AF:
0.00105
Gnomad4 ASJ exome
AF:
0.00785
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.000115
Gnomad4 FIN exome
AF:
0.00419
Gnomad4 NFE exome
AF:
0.00429
Gnomad4 OTH exome
AF:
0.00291
GnomAD4 genome
AF:
0.00268
AC:
407
AN:
152134
Hom.:
2
Cov.:
32
AF XY:
0.00243
AC XY:
181
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.000651
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.00721
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00294
Gnomad4 NFE
AF:
0.00451
Gnomad4 OTH
AF:
0.00332
Alfa
AF:
0.00429
Hom.:
2
Bravo
AF:
0.00235
TwinsUK
AF:
0.00620
AC:
23
ALSPAC
AF:
0.00337
AC:
13
ESP6500AA
AF:
0.000273
AC:
1
ESP6500EA
AF:
0.00391
AC:
32
ExAC
AF:
0.00397
AC:
480
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenOct 01, 2024MIA3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.079
T
BayesDel_noAF
Uncertain
0.12
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T;.
Eigen
Uncertain
0.28
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.81
T;T
M_CAP
Pathogenic
0.43
D
MetaRNN
Benign
0.017
T;T
MetaSVM
Uncertain
0.32
D
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-3.9
D;D
REVEL
Pathogenic
0.65
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.0030
D;D
Polyphen
0.97
D;.
Vest4
0.71
MVP
0.87
MPC
2.2
ClinPred
0.045
T
GERP RS
4.6
Varity_R
0.45
gMVP
0.12

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs193055682; hg19: chr1-222800921; COSMIC: COSV99049271; COSMIC: COSV99049271; API