Genetic Variant NM_021242.6:c.545G>A (chrX-38805491-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021242.6(MID1IP1):c.545G>A(p.Gly182Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00349 in 1,204,749 control chromosomes in the GnomAD database, including 9 homozygotes. There are 1,329 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 0 hom., 78 hem., cov: 21)

Exomes 𝑓: 0.0035 ( 9 hom. 1251 hem. )

Consequence

MID1IP1
NM_021242.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.06

Publications

7 publications found

Variant links:

Genes affected

MID1IP1 (HGNC:20715): (MID1 interacting protein 1) Predicted to enable identical protein binding activity and protein C-terminus binding activity. Predicted to be involved in several processes, including negative regulation of microtubule depolymerization; positive regulation of fatty acid biosynthetic process; and protein polymerization. Predicted to be located in cytoplasm and microtubule cytoskeleton. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

MID1IP1 links:

MID1IP1-AS1 (HGNC:40932): (MID1IP1 antisense RNA 1)

MID1IP1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007916033).

BP6

Variant X-38805491-G-A is Benign according to our data. Variant chrX-38805491-G-A is described in ClinVar as Benign. ClinVar VariationId is 711083.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 78 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021242.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MID1IP1	NM_021242.6	MANE Select	c.545G>A	p.Gly182Asp	missense	Exon 3 of 3	NP_067065.1	Q9NPA3
MID1IP1	NM_001098790.2		c.545G>A	p.Gly182Asp	missense	Exon 3 of 3	NP_001092260.1	Q9NPA3
MID1IP1	NM_001098791.2		c.545G>A	p.Gly182Asp	missense	Exon 2 of 2	NP_001092261.1	Q9NPA3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MID1IP1	ENST00000614558.3	TSL:5 MANE Select	c.545G>A	p.Gly182Asp	missense	Exon 3 of 3	ENSP00000483547.1	Q9NPA3
MID1IP1	ENST00000336949.7	TSL:1	c.545G>A	p.Gly182Asp	missense	Exon 2 of 2	ENSP00000338706.6	Q9NPA3
MID1IP1	ENST00000378474.3	TSL:1	c.545G>A	p.Gly182Asp	missense	Exon 3 of 3	ENSP00000367735.3	Q9NPA3

Frequencies

GnomAD3 genomes

AF:

0.00311

AC:

336

AN:

108120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00444

Gnomad AMR

AF:

0.00854

Gnomad ASJ

AF:

0.00918

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000195

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00388

Gnomad OTH

AF:

0.00554

GnomAD2 exomes

AF:

0.00284

AC:

512

AN:

180016

AF XY:

0.00291

show subpopulations

Gnomad AFR exome

AF:

0.000237

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.0103

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000506

Gnomad NFE exome

AF:

0.00414

Gnomad OTH exome

AF:

0.00584

GnomAD4 exome

AF:

0.00353

AC:

3870

AN:

1096599

Hom.:

Cov.:

AF XY:

0.00346

AC XY:

1251

AN XY:

362071

show subpopulations

African (AFR)

AF:

0.000303

AC:

AN:

26385

American (AMR)

AF:

0.00327

AC:

115

AN:

35189

Ashkenazi Jewish (ASJ)

AF:

0.0117

AC:

227

AN:

19362

East Asian (EAS)

AF:

0.00

AC:

AN:

30193

South Asian (SAS)

AF:

0.00

AC:

AN:

54086

European-Finnish (FIN)

AF:

0.000620

AC:

AN:

40327

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4128

European-Non Finnish (NFE)

AF:

0.00396

AC:

3332

AN:

840902

Other (OTH)

AF:

0.00354

AC:

163

AN:

46027

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

140

279

419

558

698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

122

244

366

488

610

<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:

0.00311

AC:

336

AN:

108150

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

AN XY:

30532

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

29669

American (AMR)

AF:

0.00853

AC:

AN:

10203

Ashkenazi Jewish (ASJ)

AF:

0.00918

AC:

AN:

2615

East Asian (EAS)

AF:

0.00

AC:

AN:

3339

South Asian (SAS)

AF:

0.00

AC:

AN:

2484

European-Finnish (FIN)

AF:

0.000195

AC:

AN:

5131

Middle Eastern (MID)

AF:

0.00

AC:

AN:

209

European-Non Finnish (NFE)

AF:

0.00388

AC:

203

AN:

52361

Other (OTH)

AF:

0.00547

AC:

AN:

1463

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00369

Hom.:

165

Bravo

AF:

0.00408

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00381

AC:

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.00372

AC:

ExAC

AF:

0.00280

AC:

340

EpiCase

AF:

0.00278

EpiControl

AF:

0.00488

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.49

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.0079

MetaSVM

Uncertain

-0.20

MutationAssessor

Uncertain

2.4

PhyloP100

3.1

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.63

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.41

MVP

0.74

MPC

1.3

ClinPred

0.043

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.63

gMVP

0.74

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over