chr19-40775652-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_006533.4(MIA):c.110C>T(p.Ala37Val) variant causes a missense change. The variant allele was found at a frequency of 0.000479 in 1,614,066 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 2 hom. )

Consequence

MIA
NM_006533.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.54

Publications

3 publications found

Variant links:

Genes affected

MIA (HGNC:7076): (MIA SH3 domain containing) Predicted to enable growth factor activity. Predicted to be involved in extracellular matrix organization. Predicted to act upstream of or within cell-matrix adhesion. Predicted to be located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

MIA links:

MIA-RAB4B (HGNC:48352): (MIA-RAB4B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring MIA (melanoma inhibitory activity) and RAB4B (RAB4B, member RAS oncogene family) genes on chromosome 19. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

MIA-RAB4B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01411593).

BP6

Variant 19-40775652-C-T is Benign according to our data. Variant chr19-40775652-C-T is described in ClinVar as Benign. ClinVar VariationId is 3038439.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006533.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIA	NM_006533.4	MANE Select	c.110C>T	p.Ala37Val	missense	Exon 1 of 4	NP_006524.1	Q16674-1
MIA	NM_001202553.2		c.110C>T	p.Ala37Val	missense	Exon 2 of 5	NP_001189482.1	Q16674-1
MIA-RAB4B	NR_037775.1		n.116C>T		non_coding_transcript_exon	Exon 1 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIA	ENST00000263369.4	TSL:1 MANE Select	c.110C>T	p.Ala37Val	missense	Exon 1 of 4	ENSP00000263369.2	Q16674-1
MIA-RAB4B	ENST00000600729.2	TSL:5	n.110C>T		non_coding_transcript_exon	Exon 2 of 11	ENSP00000472384.1	W4VSR3
MIA	ENST00000594436.5	TSL:2	c.110C>T	p.Ala37Val	missense	Exon 2 of 5	ENSP00000470129.1	Q16674-1

Frequencies

GnomAD3 genomes

AF:

0.00247

AC:

376

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00887

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000601

AC:

151

AN:

251438

AF XY:

0.000449

show subpopulations

Gnomad AFR exome

AF:

0.00775

Gnomad AMR exome

AF:

0.000549

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000270

AC:

394

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000238

AC XY:

173

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00869

AC:

291

AN:

33480

American (AMR)

AF:

0.000626

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000261

AC:

AN:

1112010

Other (OTH)

AF:

0.000662

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

101

126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.00249

AC:

379

AN:

152178

Hom.:

Cov.:

AF XY:

0.00253

AC XY:

188

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.00891

AC:

370

AN:

41506

American (AMR)

AF:

0.000393

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68004

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000917

Hom.:

Bravo

AF:

0.00310

ESP6500AA

AF:

0.00817

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000741

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MIA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.61

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

MetaRNN

Benign

0.014

MetaSVM

Uncertain

0.22

MutationAssessor

Pathogenic

2.9

PhyloP100

5.5

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.6

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.75

MVP

0.87

MPC

0.83

ClinPred

0.036

GERP RS

4.7

PromoterAI

0.0024

Neutral

(source)

Varity_R

0.43

gMVP

0.75

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over