Variant 14-37268777-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001388067.1(MIPOL1):c.371G>A(p.Arg124Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,429,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MIPOL1
NM_001388067.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.41

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:

MIPOL1 (HGNC:):

MIPOL1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09711406).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIPOL1	NM_001388067.1 linkuse as main transcript	c.371G>A	p.Arg124Lys	missense_variant	5/13	ENST00000684589.1	NP_001374996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIPOL1	ENST00000684589.1 linkuse as main transcript	c.371G>A	p.Arg124Lys	missense_variant	5/13		NM_001388067.1	ENSP00000506738.1		Q8TD10-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1429198

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

711376

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000183

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2024

The c.371G>A (p.R124K) alteration is located in exon 7 (coding exon 3) of the MIPOL1 gene. This alteration results from a G to A substitution at nucleotide position 371, causing the arginine (R) at amino acid position 124 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.048

T;T;T;T;T;T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.057

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.65

.;.;T;.;T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.097

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;.;.;.;.;L

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.39

N;N;N;N;N;N;N

REVEL

Benign

0.053

Sift

Benign

0.35

T;T;T;T;T;T;T

Sift4G

Benign

0.68

T;T;T;T;T;T;T

Polyphen

0.039

B;B;.;B;.;B;B

Vest4

0.24

MutPred

0.17

Gain of ubiquitination at R124 (P = 0.0494);Gain of ubiquitination at R124 (P = 0.0494);.;.;Gain of ubiquitination at R124 (P = 0.0494);.;Gain of ubiquitination at R124 (P = 0.0494);

MVP

0.58

MPC

0.033

ClinPred

0.46

GERP RS

3.6

Varity_R

0.097

gMVP

0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over