Genetic Variant NM_001388067.1:c.529C>T (chr14-37285353-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001388067.1(MIPOL1):c.529C>T(p.Arg177Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,613,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

MIPOL1
NM_001388067.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18

Publications

3 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: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.819

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.529C>T	p.Arg177Cys	missense	Exon 7 of 13	NP_001374996.1	Q8TD10-1
MIPOL1	NM_001388069.1		c.529C>T	p.Arg177Cys	missense	Exon 7 of 13	NP_001374998.1	A0A8Q3SHY7
MIPOL1	NM_001195296.2		c.529C>T	p.Arg177Cys	missense	Exon 9 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.529C>T	p.Arg177Cys	missense	Exon 7 of 13	ENSP00000506738.1	Q8TD10-1
MIPOL1	ENST00000327441.11	TSL:1	c.529C>T	p.Arg177Cys	missense	Exon 8 of 14	ENSP00000333539.7	Q8TD10-1
MIPOL1	ENST00000396294.7	TSL:1	c.529C>T	p.Arg177Cys	missense	Exon 9 of 15	ENSP00000379589.2	Q8TD10-1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

151922

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000597

AC:

AN:

251358

AF XY:

0.0000442

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000410

AC:

AN:

1461786

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33478

American (AMR)

AF:

0.0000894

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

1111940

Other (OTH)

AF:

0.0000497

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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:

0.0000592

AC:

AN:

151922

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74174

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41342

American (AMR)

AF:

0.000131

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68000

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.000132

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

Uncertain

0.44

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Pathogenic

0.21

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.38

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.095

MetaRNN

Pathogenic

0.82

MetaSVM

Uncertain

-0.18

MutationAssessor

Uncertain

2.5

PhyloP100

3.2

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-5.6

REVEL

Uncertain

0.33

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.92

MVP

0.87

MPC

0.24

ClinPred

0.87

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.50

gMVP

0.54

Mutation Taster

=77/23

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