chr19-1254317-C-T

Variant names:

• chr19-1254317-C-T
• rs1338724071
• NM_001388306.1:c.664C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001388306.1(MIDN):​c.664C>T​(p.Arg222Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000494 in 1,418,380 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R222Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: MIDN NM_001388306.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.68
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24458739).

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.664C>T	p.Arg222Trp	missense	Exon 6 of 9	NP_001375235.1	A0A804HKJ8
	MIDN	NM_001388474.1		c.535C>T	p.Arg179Trp	missense	Exon 4 of 7	NP_001375403.1	Q504T8
	MIDN	NM_177401.5		c.535C>T	p.Arg179Trp	missense	Exon 5 of 8	NP_796375.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIDN	ENST00000682408.1	MANE Select	c.664C>T	p.Arg222Trp	missense	Exon 6 of 9	ENSP00000507955.1	A0A804HKJ8
	MIDN	ENST00000591446.7	TSL:1	c.535C>T	p.Arg179Trp	missense	Exon 4 of 7	ENSP00000467679.1	Q504T8
	MIDN	ENST00000937331.1		c.664C>T	p.Arg222Trp	missense	Exon 6 of 9	ENSP00000607390.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000494 AC: 7 AN: 1418380 Hom.: 0 Cov.: 34 AF XY: 0.00000568 AC XY: 4 AN XY: 703746

African (AFR) AF: 0.0000310 AC: 1 AN: 32278

American (AMR) AF: 0.00 AC: 0 AN: 41106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25192

East Asian (EAS) AF: 0.00 AC: 0 AN: 38198

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5648

European-Non Finnish (NFE) AF: 0.00000456 AC: 5 AN: 1097432

Other (OTH) AF: 0.00 AC: 0 AN: 58866

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

Asia WGS AF: 0.000289 AC: 1 AN: 3476

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	Benign	0.22
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.43	N
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	M
PhyloP100		3.7
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.12
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.047	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.26		Gain of catalytic residue at P182 (P = 0.0235)
MVP		0.34
MPC		0.69
ClinPred		0.82	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.25
Mutation Taster		=88/12	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: rs1338724071; hg19: chr19-1254316;