Variant 19-1254305-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_001388306.1(MIDN):c.652G>A(p.Ala218Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,567,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00071 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

MIDN
NM_001388306.1 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.04

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:

MIDN (HGNC:):

MIDN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0057910085).

BP6

Variant 19-1254305-G-A is Benign according to our data. Variant chr19-1254305-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3045946.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIDN	NM_001388306.1 linkuse as main transcript	c.652G>A	p.Ala218Thr	missense_variant	6/9	ENST00000682408.1	NP_001375235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MIDN	ENST00000682408.1 linkuse as main transcript	c.652G>A	p.Ala218Thr	missense_variant	6/9		NM_001388306.1	ENSP00000507955.1	A0A804HKJ8
MIDN	ENST00000591446.7 linkuse as main transcript	c.523G>A	p.Ala175Thr	missense_variant	4/7	1		ENSP00000467679.1	Q504T8
MIDN	ENST00000300952.7 linkuse as main transcript	c.523G>A	p.Ala175Thr	missense_variant	5/8	5		ENSP00000300952.2	Q504T8
MIDN	ENST00000590136.1 linkuse as main transcript	n.*2G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000703

AC:

107

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

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:

0.0000294

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000201

AC:

AN:

183678

Hom.:

AF XY:

0.000165

AC XY:

AN XY:

102930

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.000306

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:

0.0000247

Gnomad OTH exome

AF:

0.000212

GnomAD4 exome

AF:

0.0000791

AC:

112

AN:

1415726

Hom.:

Cov.:

AF XY:

0.0000712

AC XY:

AN XY:

702318

show subpopulations

Gnomad4 AFR exome

AF:

0.00216

Gnomad4 AMR exome

AF:

0.000347

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:

0.0000155

Gnomad4 OTH exome

AF:

0.000153

GnomAD4 genome

AF:

0.000709

AC:

108

AN:

152228

Hom.:

Cov.:

AF XY:

0.000699

AC XY:

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00229

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000347

Hom.:

Bravo

AF:

0.000767

ESP6500AA

AF:

0.00267

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000217

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MIDN-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 18, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;T;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.80

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.68

T;T;.

M_CAP

Benign

0.023

MetaRNN

Benign

0.0058

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

.;L;L

MutationTaster

Benign

0.90

D;D

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.56

.;N;.

REVEL

Benign

0.088

Sift

Benign

0.080

.;T;.

Sift4G

Benign

0.59

T;T;T

Polyphen

0.0050

.;B;B

Vest4

0.26, 0.26

MVP

0.12

MPC

0.52

ClinPred

0.024

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.052

gMVP

0.21

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