Variant 19-1250527-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001388306.1(MIDN):c.231C>A(p.Asp77Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000672 in 148,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MIDN
NM_001388306.1 missense, splice_region

Scores

Splicing: ADA: 0.0005412

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0890

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.057926655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIDN	NM_001388306.1 linkuse as main transcript	c.231C>A	p.Asp77Glu	missense_variant, splice_region_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.231C>A	p.Asp77Glu	missense_variant, splice_region_variant	2/9		NM_001388306.1	ENSP00000507955	A2
MIDN	ENST00000591446.7 linkuse as main transcript	c.231C>A	p.Asp77Glu	missense_variant, splice_region_variant	1/7	1		ENSP00000467679	P2
MIDN	ENST00000300952.7 linkuse as main transcript	c.231C>A	p.Asp77Glu	missense_variant, splice_region_variant	2/8	5		ENSP00000300952	P2

Frequencies

GnomAD3 genomes

AF:

0.00000672

AC:

AN:

148782

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000394

AC:

AN:

127036

Hom.:

AF XY:

0.0000271

AC XY:

AN XY:

73888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000739

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1101382

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

532938

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000672

AC:

AN:

148782

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72492

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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

Dec 14, 2023

The c.231C>A (p.D77E) alteration is located in exon 2 (coding exon 1) of the MIDN gene. This alteration results from a C to A substitution at nucleotide position 231, causing the aspartic acid (D) at amino acid position 77 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.068

.;T;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.74

T;T;.

M_CAP

Pathogenic

0.95

MetaRNN

Benign

0.058

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.10

.;N;N

MutationTaster

Benign

0.97

N;N

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

0.55

.;N;.

REVEL

Benign

0.13

Sift

Benign

1.0

.;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0020

.;B;B

Vest4

0.054, 0.052

MutPred

0.11

Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);

MVP

0.50

MPC

0.25

ClinPred

0.084

GERP RS

1.6

Varity_R

0.070

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00054

dbscSNV1_RF

Benign

0.11

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