Genetic Variant MIDN:p.Arg209Gly (chr19-1254278-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001388306.1(MIDN):c.625C>G(p.Arg209Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,429,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

MIDN
NM_001388306.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.44

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23429117).

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.625C>G	p.Arg209Gly	missense	Exon 6 of 9	NP_001375235.1	A0A804HKJ8
MIDN	NM_001388474.1		c.496C>G	p.Arg166Gly	missense	Exon 4 of 7	NP_001375403.1	Q504T8
MIDN	NM_177401.5		c.496C>G	p.Arg166Gly	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.625C>G	p.Arg209Gly	missense	Exon 6 of 9	ENSP00000507955.1	A0A804HKJ8
MIDN	ENST00000591446.7	TSL:1	c.496C>G	p.Arg166Gly	missense	Exon 4 of 7	ENSP00000467679.1	Q504T8
MIDN	ENST00000937331.1		c.625C>G	p.Arg209Gly	missense	Exon 6 of 9	ENSP00000607390.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000299

AC:

AN:

200638

AF XY:

0.0000267

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000112

AC:

AN:

1429432

Hom.:

Cov.:

AF XY:

0.0000169

AC XY:

AN XY:

710284

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32514

American (AMR)

AF:

0.00

AC:

AN:

42470

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25522

East Asian (EAS)

AF:

0.00

AC:

AN:

38686

South Asian (SAS)

AF:

0.000189

AC:

AN:

84434

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37744

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103064

Other (OTH)

AF:

0.00

AC:

AN:

59296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

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

Cov.:

ExAC

AF:

0.0000427

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

Benign

0.24

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Benign

0.12

Eigen_PC

Benign

0.034

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.83

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.2

PhyloP100

1.4

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.8

REVEL

Benign

0.13

Sift

Uncertain

0.0020

Sift4G

Benign

0.13

Polyphen

1.0

Vest4

0.29

MutPred

0.47

Gain of loop (P = 0.0079)

MVP

0.51

MPC

0.47

ClinPred

0.23

GERP RS

1.3

Varity_R

0.48

gMVP

0.48

Mutation Taster

=31/69

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

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