NM_001388306.1:c.691G>A

Variant summary

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

The NM_001388306.1(MIDN):​c.691G>A​(p.Val231Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,565,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V231L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

MIDN
NM_001388306.1 missense

Scores

1
1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.89
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]

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=0.057482213).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MIDNNM_001388306.1 linkc.691G>A p.Val231Met missense_variant Exon 6 of 9 ENST00000682408.1 NP_001375235.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MIDNENST00000682408.1 linkc.691G>A p.Val231Met missense_variant Exon 6 of 9 NM_001388306.1 ENSP00000507955.1 A0A804HKJ8

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000349
AC:
6
AN:
172094
Hom.:
0
AF XY:
0.0000210
AC XY:
2
AN XY:
95206
show subpopulations
Gnomad AFR exome
AF:
0.000100
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000685
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000198
AC:
28
AN:
1413194
Hom.:
0
Cov.:
34
AF XY:
0.0000214
AC XY:
15
AN XY:
700796
show subpopulations
Gnomad4 AFR exome
AF:
0.0000308
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000243
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000228
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152296
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.0000240
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ExAC
AF:
0.0000259
AC:
3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
14
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
.;T;T
Eigen
Benign
-0.99
Eigen_PC
Benign
-0.97
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.72
T;T;.
M_CAP
Benign
0.071
D
MetaRNN
Benign
0.057
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
.;L;L
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-0.93
.;N;.
REVEL
Benign
0.078
Sift
Benign
0.085
.;T;.
Sift4G
Benign
0.23
T;T;T
Polyphen
0.017
.;B;B
Vest4
0.20, 0.20
MutPred
0.054
Loss of glycosylation at S189 (P = 0.1107);Loss of glycosylation at S189 (P = 0.1107);Loss of glycosylation at S189 (P = 0.1107);
MVP
0.14
MPC
0.62
ClinPred
0.044
T
GERP RS
1.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3
Varity_R
0.062
gMVP
0.15

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs748612554; hg19: chr19-1254343; API