rs775440270

Variant names:

• chr19-1250402-C-T
• rs775440270
• NM_001388306.1:c.106C>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.106C>T​(p.His36Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,320,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: MIDN NM_001388306.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.723
• 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=0.1408974).

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.106C>T	p.His36Tyr	missense	Exon 2 of 9	NP_001375235.1	A0A804HKJ8
	MIDN	NM_001388474.1		c.106C>T	p.His36Tyr	missense	Exon 1 of 7	NP_001375403.1	Q504T8
	MIDN	NM_177401.5		c.106C>T	p.His36Tyr	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.106C>T	p.His36Tyr	missense	Exon 2 of 9	ENSP00000507955.1	A0A804HKJ8
	MIDN	ENST00000591446.7	TSL:1	c.106C>T	p.His36Tyr	missense	Exon 1 of 7	ENSP00000467679.1	Q504T8
	MIDN	ENST00000937331.1		c.106C>T	p.His36Tyr	missense	Exon 2 of 9	ENSP00000607390.1

Frequencies

GnomAD3 genomes AF: 0.0000337 AC: 5 AN: 148564 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000201

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: 0.000487

GnomAD2 exomes AF: 0.0000200 AC: 3 AN: 149884 AF XY: 0.0000116

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: 0.0000434

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000307 AC: 36 AN: 1172316 Hom.: 0 Cov.: 30 AF XY: 0.0000225 AC XY: 13 AN XY: 578266

African (AFR) AF: 0.00 AC: 0 AN: 24224

American (AMR) AF: 0.0000693 AC: 2 AN: 28858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17344

East Asian (EAS) AF: 0.00 AC: 0 AN: 22968

South Asian (SAS) AF: 0.00 AC: 0 AN: 53426

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3790

European-Non Finnish (NFE) AF: 0.0000358 AC: 34 AN: 948424

Other (OTH) AF: 0.00 AC: 0 AN: 43652

GnomAD4 genome AF: 0.0000336 AC: 5 AN: 148672 Hom.: 0 Cov.: 32 AF XY: 0.0000414 AC XY: 3 AN XY: 72532

African (AFR) AF: 0.00 AC: 0 AN: 41198

American (AMR) AF: 0.000200 AC: 3 AN: 14974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3416

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66706

Other (OTH) AF: 0.000482 AC: 1 AN: 2074

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.00000848 AC: 1

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	0.16
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.47	N
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.63	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.72
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.071
Sift	Benign	0.40	T
Sift4G	Benign	0.98	T
Polyphen		0.67	P
Vest4		0.17
MutPred		0.23		Gain of phosphorylation at H36 (P = 0.0337)
MVP		0.31
MPC		0.60
ClinPred		0.35	T
GERP RS		1.5
Varity_R		0.12
gMVP		0.44
Mutation Taster		=85/15	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: rs775440270; hg19: chr19-1250401;