Variant 19-1250460-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001388306.1(MIDN):c.164G>A(p.Gly55Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000367 in 1,388,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

MIDN
NM_001388306.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.68

Variant links:

Genes affected

MIDN (HGNC:16298): (midnolin) Predicted to enable kinase binding activity. Predicted to be involved in negative regulation of glucokinase activity and negative regulation of insulin secretion. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MIDN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3583411).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIDN	NM_001388306.1 linkuse as main transcript	c.164G>A	p.Gly55Glu	missense_variant	2/9	ENST00000682408.1	NP_001375235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MIDN	ENST00000682408.1 linkuse as main transcript	c.164G>A	p.Gly55Glu	missense_variant	2/9		NM_001388306.1	ENSP00000507955	A2
MIDN	ENST00000591446.7 linkuse as main transcript	c.164G>A	p.Gly55Glu	missense_variant	1/7	1		ENSP00000467679	P2
MIDN	ENST00000300952.7 linkuse as main transcript	c.164G>A	p.Gly55Glu	missense_variant	2/8	5		ENSP00000300952	P2

Frequencies

GnomAD3 genomes

AF:

0.0000336

AC:

AN:

149008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

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:

0.0000599

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000170

AC:

AN:

176140

Hom.:

AF XY:

0.00000998

AC XY:

AN XY:

100226

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000371

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000371

AC:

AN:

1239520

Hom.:

Cov.:

AF XY:

0.0000374

AC XY:

AN XY:

614556

show subpopulations

Gnomad4 AFR exome

AF:

0.0000390

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:

0.0000438

Gnomad4 OTH exome

AF:

0.0000424

GnomAD4 genome

AF:

0.0000336

AC:

AN:

149008

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

72628

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000599

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000298

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000252

AC:

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

Mar 14, 2023

The c.164G>A (p.G55E) alteration is located in exon 2 (coding exon 1) of the MIDN gene. This alteration results from a G to A substitution at nucleotide position 164, causing the glycine (G) at amino acid position 55 to be replaced by a glutamic acid (E). 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

Pathogenic

0.75

BayesDel_addAF

Benign

-0.0078

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

.;T;T

Eigen

Benign

0.13

Eigen_PC

Benign

0.081

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.86

D;D;.

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

0.96

.;L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-1.9

.;N;.

REVEL

Uncertain

0.29

Sift

Benign

0.29

.;T;.

Sift4G

Benign

0.33

T;T;T

Polyphen

1.0

.;D;D

Vest4

0.22

MutPred

0.25

Gain of ubiquitination at K58 (P = 0.0355);Gain of ubiquitination at K58 (P = 0.0355);Gain of ubiquitination at K58 (P = 0.0355);

MVP

0.80

MPC

0.50

ClinPred

0.48

GERP RS

2.7

Varity_R

0.24

gMVP

0.65

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