Genetic Variant NM_001388306.1:c.595C>T (chr19-1254248-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001388306.1(MIDN):c.595C>T(p.Leu199Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L199V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MIDN
NM_001388306.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.02

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38302442).

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.595C>T	p.Leu199Phe	missense	Exon 6 of 9	NP_001375235.1	A0A804HKJ8
MIDN	NM_001388474.1		c.466C>T	p.Leu156Phe	missense	Exon 4 of 7	NP_001375403.1	Q504T8
MIDN	NM_177401.5		c.466C>T	p.Leu156Phe	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.595C>T	p.Leu199Phe	missense	Exon 6 of 9	ENSP00000507955.1	A0A804HKJ8
MIDN	ENST00000591446.7	TSL:1	c.466C>T	p.Leu156Phe	missense	Exon 4 of 7	ENSP00000467679.1	Q504T8
MIDN	ENST00000937331.1		c.595C>T	p.Leu199Phe	missense	Exon 6 of 9	ENSP00000607390.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1441070

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716954

African (AFR)

AF:

0.00

AC:

AN:

33046

American (AMR)

AF:

0.00

AC:

AN:

44120

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25866

East Asian (EAS)

AF:

0.00

AC:

AN:

39280

South Asian (SAS)

AF:

0.00

AC:

AN:

85358

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108404

Other (OTH)

AF:

0.00

AC:

AN:

59868

GnomAD4 genome

Cov.:

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

1.0

BayesDel_addAF

Uncertain

0.043

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.75

Eigen

Benign

0.15

Eigen_PC

Benign

0.025

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.88

M_CAP

Pathogenic

0.29

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.4

PhyloP100

1.0

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.18

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.69

MutPred

0.40

Loss of helix (P = 3e-04)

MVP

0.28

MPC

0.63

ClinPred

0.97

GERP RS

1.4

Varity_R

0.49

gMVP

0.58

Mutation Taster

=35/65

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over