dbSNP rs17465637: MIA3:c.3632-105A>C (chr1-222650187-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198551.4(MIA3):c.3632-105A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 736,816 control chromosomes in the GnomAD database, including 165,801 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 0.57 ( 28044 hom., cov: 32)

Exomes 𝑓: 0.68 ( 137757 hom. )

Consequence

MIA3
NM_198551.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.629

Publications

199 publications found

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]

MIA3 Gene-Disease associations (from GenCC):

odontochondrodysplasia 2 with hearing loss and diabetes
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

MIA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIA3	NM_198551.4 link	c.3632-105A>C		intron_variant	Intron 8 of 27	ENST00000344922.10	NP_940953.2	Q5JRA6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIA3	ENST00000344922.10 link	c.3632-105A>C		intron_variant	Intron 8 of 27	5	NM_198551.4	ENSP00000340900.5		Q5JRA6-1

Frequencies

GnomAD3 genomes

AF:

0.572

AC:

86881

AN:

151940

Hom.:

28034

Cov.:

show subpopulations

Gnomad AFR

AF:

0.258

Gnomad AMI

AF:

0.781

Gnomad AMR

AF:

0.559

Gnomad ASJ

AF:

0.715

Gnomad EAS

AF:

0.595

Gnomad SAS

AF:

0.603

Gnomad FIN

AF:

0.750

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.723

Gnomad OTH

AF:

0.586

GnomAD2 exomes

AF:

0.643

AC:

99728

AN:

155216

AF XY:

0.651

show subpopulations

Gnomad AFR exome

AF:

0.249

Gnomad AMR exome

AF:

0.496

Gnomad ASJ exome

AF:

0.717

Gnomad EAS exome

AF:

0.596

Gnomad FIN exome

AF:

0.748

Gnomad NFE exome

AF:

0.725

Gnomad OTH exome

AF:

0.658

GnomAD4 exome

AF:

0.679

AC:

396789

AN:

584758

Hom.:

137757

Cov.:

AF XY:

0.681

AC XY:

214251

AN XY:

314462

show subpopulations

African (AFR)

AF:

0.262

AC:

4148

AN:

15856

American (AMR)

AF:

0.498

AC:

16896

AN:

33938

Ashkenazi Jewish (ASJ)

AF:

0.719

AC:

14142

AN:

19672

East Asian (EAS)

AF:

0.562

AC:

17622

AN:

31364

South Asian (SAS)

AF:

0.630

AC:

38967

AN:

61870

European-Finnish (FIN)

AF:

0.747

AC:

34982

AN:

46846

Middle Eastern (MID)

AF:

0.668

AC:

2679

AN:

4012

European-Non Finnish (NFE)

AF:

0.726

AC:

246984

AN:

340324

Other (OTH)

AF:

0.660

AC:

20369

AN:

30876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

6244

12489

18733

24978

31222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1620

3240

4860

6480

8100

<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:

0.571

AC:

86897

AN:

152058

Hom.:

28044

Cov.:

AF XY:

0.573

AC XY:

42603

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.257

AC:

10674

AN:

41458

American (AMR)

AF:

0.559

AC:

8536

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.715

AC:

2482

AN:

3470

East Asian (EAS)

AF:

0.596

AC:

3081

AN:

5168

South Asian (SAS)

AF:

0.604

AC:

2910

AN:

4818

European-Finnish (FIN)

AF:

0.750

AC:

7935

AN:

10582

Middle Eastern (MID)

AF:

0.650

AC:

191

AN:

294

European-Non Finnish (NFE)

AF:

0.723

AC:

49141

AN:

67974

Other (OTH)

AF:

0.587

AC:

1236

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1597

3195

4792

6390

7987

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

718

1436

2154

2872

3590

<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:

0.671

Hom.:

150448

Bravo

AF:

0.541

Asia WGS

AF:

0.545

AC:

1897

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.059

(source)

DANN

Benign

0.56

PhyloP100

-0.63

Mutation Taster

=100/0

polymorphism (auto)

(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

Computational scores

Splicing

Publications

Other links and lift over