Variant 19-1250528-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001388306.1(MIDN):c.232A>G(p.Thr78Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,095,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 9.1e-7 ( 0 hom. )

Consequence

MIDN
NM_001388306.1 missense, splice_region

Scores

Splicing: ADA: 0.9954

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.40

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIDN	NM_001388306.1 link	c.232A>G	p.Thr78Ala	missense_variant, splice_region_variant	2/9	ENST00000682408.1	NP_001375235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MIDN	ENST00000682408.1 link	c.232A>G	p.Thr78Ala	missense_variant, splice_region_variant	2/9		NM_001388306.1	ENSP00000507955.1	A0A804HKJ8
MIDN	ENST00000591446.7 link	c.232A>G	p.Thr78Ala	missense_variant, splice_region_variant	1/7	1		ENSP00000467679.1	Q504T8
MIDN	ENST00000300952.7 link	c.232A>G	p.Thr78Ala	missense_variant, splice_region_variant	2/8	5		ENSP00000300952.2	Q504T8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.12e-7

AC:

AN:

1095936

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

530324

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:

0.00000111

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 03, 2023

The c.232A>G (p.T78A) alteration is located in exon 2 (coding exon 1) of the MIDN gene. This alteration results from a A to G substitution at nucleotide position 232, causing the threonine (T) at amino acid position 78 to be replaced by an alanine (A). 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

0.20

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.17

.;T;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.72

T;T;.

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.0

.;M;M

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.2

.;N;.

REVEL

Benign

0.14

Sift

Benign

0.24

.;T;.

Sift4G

Benign

0.36

T;T;T

Polyphen

0.0020

.;B;B

Vest4

0.17, 0.17

MutPred

0.12

Loss of phosphorylation at T78 (P = 0.0654);Loss of phosphorylation at T78 (P = 0.0654);Loss of phosphorylation at T78 (P = 0.0654);

MVP

0.70

MPC

0.29

ClinPred

0.38

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.84

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.23

Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over