19-1250486-C-T

Variant names:

• chr19-1250486-C-T
• rs763117290
• NM_001388306.1:c.190C>T

Variant summary

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

The NM_001388306.1(MIDN):​c.190C>T​(p.Leu64Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000249 in 1,365,654 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L64I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: MIDN NM_001388306.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.22
• Publications: 0 publications found

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]

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIDN	NM_001388306.1	MANE Select	c.190C>T	p.Leu64Phe	missense	Exon 2 of 9	NP_001375235.1	A0A804HKJ8
	MIDN	NM_001388474.1		c.190C>T	p.Leu64Phe	missense	Exon 1 of 7	NP_001375403.1	Q504T8
	MIDN	NM_177401.5		c.190C>T	p.Leu64Phe	missense	Exon 2 of 8	NP_796375.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIDN	ENST00000682408.1	MANE Select	c.190C>T	p.Leu64Phe	missense	Exon 2 of 9	ENSP00000507955.1	A0A804HKJ8
	MIDN	ENST00000591446.7	TSL:1	c.190C>T	p.Leu64Phe	missense	Exon 1 of 7	ENSP00000467679.1	Q504T8
	MIDN	ENST00000937331.1		c.190C>T	p.Leu64Phe	missense	Exon 2 of 9	ENSP00000607390.1

Frequencies

GnomAD3 genomes AF: 0.00000671 AC: 1 AN: 148948 Hom.: 0 Cov.: 32

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: 0.0000150

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000405 AC: 7 AN: 172632 AF XY: 0.0000305

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: 0.0000752

Gnomad OTH exome AF: 0.000268

GnomAD4 exome AF: 0.0000271 AC: 33 AN: 1216706 Hom.: 0 Cov.: 30 AF XY: 0.0000232 AC XY: 14 AN XY: 602182

African (AFR) AF: 0.00 AC: 0 AN: 24784

American (AMR) AF: 0.00 AC: 0 AN: 29646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18432

East Asian (EAS) AF: 0.00 AC: 0 AN: 25954

South Asian (SAS) AF: 0.00 AC: 0 AN: 58612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39870

Middle Eastern (MID) AF: 0.000221 AC: 1 AN: 4524

European-Non Finnish (NFE) AF: 0.0000310 AC: 30 AN: 969006

Other (OTH) AF: 0.0000436 AC: 2 AN: 45878

GnomAD4 genome AF: 0.00000671 AC: 1 AN: 148948 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1 AN XY: 72588

African (AFR) AF: 0.00 AC: 0 AN: 41152

American (AMR) AF: 0.00 AC: 0 AN: 15014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3420

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66748

Other (OTH) AF: 0.00 AC: 0 AN: 2050

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000168 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.99	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Uncertain	0.091	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.2
PrimateAI	Pathogenic	0.95	D
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.24
MutPred		0.19		Gain of methylation at K65 (P = 0.0279)
MVP		0.81
MPC		0.95
ClinPred		0.70	D
GERP RS		2.7
Varity_R		0.38
gMVP		0.40
Mutation Taster		=46/54	disease causing

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

Other links and lift over

dbSNP: rs763117290; hg19: chr19-1250485;