Genetic Variant MIA3:c.3632-105A>G (chr1-222650187-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_198551.4(MIA3):c.3632-105A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000171 in 585,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

MIA3
NM_198551.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-222650187-A-G is Benign according to our data. Variant chr1-222650187-A-G is described in ClinVar as Benign. ClinVar VariationId is 1684531.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198551.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MIA3	NM_198551.4	MANE Select	c.3632-105A>G	intron	N/A	NP_940953.2
MIA3	NM_001324062.2		c.3632-105A>G	intron	N/A	NP_001310991.1
MIA3	NM_001324063.2		c.3632-105A>G	intron	N/A	NP_001310992.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MIA3	ENST00000344922.10	TSL:5 MANE Select	c.3632-105A>G	intron	N/A	ENSP00000340900.5
MIA3	ENST00000340535.11	TSL:1	c.266-105A>G	intron	N/A	ENSP00000345866.7
MIA3	ENST00000354906.7	TSL:5	c.2378-105A>G	intron	N/A	ENSP00000355062.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000644

AC:

AN:

155216

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000410

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000171

AC:

AN:

585420

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

314794

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15884

American (AMR)

AF:

0.0000294

AC:

AN:

33974

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19694

East Asian (EAS)

AF:

0.00

AC:

AN:

31404

South Asian (SAS)

AF:

0.00

AC:

AN:

61904

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46886

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4022

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

340732

Other (OTH)

AF:

0.00

AC:

AN:

30920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Coronary artery disorder

Benign:1

May 12, 2022

Rasad Genetic Department, Rasad Pathobiology and Genetic Laboratory

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.066

(source)

DANN

Benign

0.75

PhyloP100

-0.63

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over