rs763117290

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-1250486-C-A
• chr19-1250486-C-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>A​(p.Leu64Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,216,702 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. L64F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000021 (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>A	p.Leu64Ile	missense	Exon 2 of 9	NP_001375235.1	A0A804HKJ8
	MIDN	NM_001388474.1		c.190C>A	p.Leu64Ile	missense	Exon 1 of 7	NP_001375403.1	Q504T8
	MIDN	NM_177401.5		c.190C>A	p.Leu64Ile	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>A	p.Leu64Ile	missense	Exon 2 of 9	ENSP00000507955.1	A0A804HKJ8
	MIDN	ENST00000591446.7	TSL:1	c.190C>A	p.Leu64Ile	missense	Exon 1 of 7	ENSP00000467679.1	Q504T8
	MIDN	ENST00000937331.1		c.190C>A	p.Leu64Ile	missense	Exon 2 of 9	ENSP00000607390.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000205 AC: 25 AN: 1216702 Hom.: 0 Cov.: 30 AF XY: 0.0000166 AC XY: 10 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: 25952

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

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4524

European-Non Finnish (NFE) AF: 0.0000248 AC: 24 AN: 969004

Other (OTH) AF: 0.0000218 AC: 1 AN: 45878

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.89
BayesDel_addAF	Benign	0.00097	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.99	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Uncertain	-0.042	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.2
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.27
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.024	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.17		Gain of methylation at K65 (P = 0.083)
MVP		0.64
MPC		0.85
ClinPred		0.93	D
GERP RS		2.7
Varity_R		0.25
gMVP		0.26
Mutation Taster		=79/21	polymorphism

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; COSMIC: COSV99960093; COSMIC: COSV99960093;