Genetic Variant MIDN:p.Ser177Leu (chr19-1254183-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001388306.1(MIDN):c.530C>T(p.Ser177Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000015 in 1,596,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

MIDN
NM_001388306.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.54

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388306.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIDN	NM_001388306.1	MANE Select	c.530C>T	p.Ser177Leu	missense	Exon 6 of 9	NP_001375235.1	A0A804HKJ8
MIDN	NM_001388474.1		c.401C>T	p.Ser134Leu	missense	Exon 4 of 7	NP_001375403.1	Q504T8
MIDN	NM_177401.5		c.401C>T	p.Ser134Leu	missense	Exon 5 of 8	NP_796375.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIDN	ENST00000682408.1	MANE Select	c.530C>T	p.Ser177Leu	missense	Exon 6 of 9	ENSP00000507955.1	A0A804HKJ8
MIDN	ENST00000591446.7	TSL:1	c.401C>T	p.Ser134Leu	missense	Exon 4 of 7	ENSP00000467679.1	Q504T8
MIDN	ENST00000937331.1		c.530C>T	p.Ser177Leu	missense	Exon 6 of 9	ENSP00000607390.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152202

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000136

AC:

AN:

221018

AF XY:

0.0000163

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000202

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000159

AC:

AN:

1444690

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

718722

show subpopulations

African (AFR)

AF:

0.0000603

AC:

AN:

33170

American (AMR)

AF:

0.0000226

AC:

AN:

44160

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25866

East Asian (EAS)

AF:

0.00

AC:

AN:

39460

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85306

European-Finnish (FIN)

AF:

0.0000236

AC:

AN:

42302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5434

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1109036

Other (OTH)

AF:

0.0000334

AC:

AN:

59956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000169

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Uncertain

0.081

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.66

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

M_CAP

Pathogenic

0.74

MetaRNN

Uncertain

0.57

MetaSVM

Benign

-0.38

MutationAssessor

Uncertain

2.3

PhyloP100

4.5

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-4.9

REVEL

Uncertain

0.32

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.94

MutPred

0.23

Loss of disorder (P = 0.0337)

MVP

0.62

MPC

0.74

ClinPred

0.98

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.70

gMVP

0.51

Mutation Taster

=9/91

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over