Genetic Variant MIPOL1:p.Pro100Ala (chr14-37268704-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001388067.1(MIPOL1):c.298C>G(p.Pro100Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000063 in 1,602,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

MIPOL1
NM_001388067.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0540

Publications

1 publications found

Variant links:

Genes affected

MIPOL1 (HGNC:21460): (mirror-image polydactyly 1) This gene encodes a coiled-coil domain-containing protein. The encoded protein may function as a tumor suppressor. A translocation that results in truncation of the protein encoded by this locus has been associated with mirror-image polydactyly, also known as Laurin-Sandrow Syndrome. Alternatively spliced transcript variants have been described. [provided by RefSeq, Sep 2010]

MIPOL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07686481).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388067.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIPOL1	NM_001388067.1	MANE Select	c.298C>G	p.Pro100Ala	missense	Exon 5 of 13	NP_001374996.1	Q8TD10-1
MIPOL1	NM_001388069.1		c.298C>G	p.Pro100Ala	missense	Exon 5 of 13	NP_001374998.1	A0A8Q3SHY7
MIPOL1	NM_001195296.2		c.298C>G	p.Pro100Ala	missense	Exon 7 of 15	NP_001182225.1	Q8TD10-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIPOL1	ENST00000684589.1	MANE Select	c.298C>G	p.Pro100Ala	missense	Exon 5 of 13	ENSP00000506738.1	Q8TD10-1
MIPOL1	ENST00000327441.11	TSL:1	c.298C>G	p.Pro100Ala	missense	Exon 6 of 14	ENSP00000333539.7	Q8TD10-1
MIPOL1	ENST00000396294.7	TSL:1	c.298C>G	p.Pro100Ala	missense	Exon 7 of 15	ENSP00000379589.2	Q8TD10-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000191

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000490

AC:

AN:

244850

AF XY:

0.0000453

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000306

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000986

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000600

AC:

AN:

1450090

Hom.:

Cov.:

AF XY:

0.0000624

AC XY:

AN XY:

721714

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32974

American (AMR)

AF:

0.00

AC:

AN:

43374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25984

East Asian (EAS)

AF:

0.00

AC:

AN:

39278

South Asian (SAS)

AF:

0.00

AC:

AN:

84746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.0000697

AC:

AN:

1104686

Other (OTH)

AF:

0.000167

AC:

AN:

59976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

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

AF:

0.0000920

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41560

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

67988

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.418

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:

0.000118

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.071

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.81

M_CAP

Benign

0.016

MetaRNN

Benign

0.077

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

-0.054

PrimateAI

Benign

0.31

PROVEAN

Pathogenic

-6.8

REVEL

Benign

0.043

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.46

Vest4

0.44

MVP

0.45

MPC

0.049

ClinPred

0.22

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.031

gMVP

0.065

Mutation Taster

=97/3

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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