19-1250493-T-G

Position:

• chr19-1250493-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001388306.1(MIDN):​c.197T>G​(p.Val66Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MIDN NM_001388306.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.52

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIDN	NM_001388306.1	c.197T>G	p.Val66Gly	missense_variant	2/9	ENST00000682408.1	NP_001375235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIDN	ENST00000682408.1	c.197T>G	p.Val66Gly	missense_variant	2/9		NM_001388306.1	ENSP00000507955.1
MIDN	ENST00000591446.7	c.197T>G	p.Val66Gly	missense_variant	1/7	1		ENSP00000467679.1
MIDN	ENST00000300952.7	c.197T>G	p.Val66Gly	missense_variant	2/8	5		ENSP00000300952.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

The c.197T>G (p.V66G) alteration is located in exon 2 (coding exon 1) of the MIDN gene. This alteration results from a T to G substitution at nucleotide position 197, causing the valine (V) at amino acid position 66 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.74	.;D;D
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.74	T;T;.
M_CAP	Pathogenic	0.99	D
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Uncertain	0.019	D
MutationAssessor	Uncertain	2.9	.;M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.93	D
PROVEAN	Pathogenic	-5.2	.;D;.
REVEL	Pathogenic	0.66
Sift	Pathogenic	0.0	.;D;.
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		0.99	.;D;D
Vest4		0.21
MutPred		0.29		Loss of stability (P = 0.0195);Loss of stability (P = 0.0195);Loss of stability (P = 0.0195);
MVP		0.92
MPC		1.0
ClinPred		1.0	D
GERP RS		2.7
Varity_R		0.89
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-1250492;