19-1250379-C-T

Variant names:

• chr19-1250379-C-T
• rs2145484307
• NM_001388306.1:c.83C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001388306.1(MIDN):​c.83C>T​(p.Ala28Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 32)
  • Exomes 𝑓: 9.6e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MIDN NM_001388306.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.12
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11446118).

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.83C>T	p.Ala28Val	missense	Exon 2 of 9	NP_001375235.1	A0A804HKJ8
	MIDN	NM_001388474.1		c.83C>T	p.Ala28Val	missense	Exon 1 of 7	NP_001375403.1	Q504T8
	MIDN	NM_177401.5		c.83C>T	p.Ala28Val	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.83C>T	p.Ala28Val	missense	Exon 2 of 9	ENSP00000507955.1	A0A804HKJ8
	MIDN	ENST00000591446.7	TSL:1	c.83C>T	p.Ala28Val	missense	Exon 1 of 7	ENSP00000467679.1	Q504T8
	MIDN	ENST00000937331.1		c.83C>T	p.Ala28Val	missense	Exon 2 of 9	ENSP00000607390.1

Frequencies

GnomAD3 genomes AF: 0.00000676 AC: 1 AN: 147970 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: 0.00

Gnomad OTH AF: 0.000490

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.55e-7 AC: 1 AN: 1046808 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 505572

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 20548

American (AMR) AF: 0.00 AC: 0 AN: 16350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14394

East Asian (EAS) AF: 0.00 AC: 0 AN: 17390

South Asian (SAS) AF: 0.0000293 AC: 1 AN: 34126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2796

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 883774

Other (OTH) AF: 0.00 AC: 0 AN: 38024

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000675 AC: 1 AN: 148078 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1 AN XY: 72224

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41094

American (AMR) AF: 0.00 AC: 0 AN: 14926

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3410

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66520

Other (OTH) AF: 0.000484 AC: 1 AN: 2064

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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	0.086
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.53	T
M_CAP	Pathogenic	0.42	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.1
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.037
Sift	Benign	0.11	T
Sift4G	Benign	0.26	T
Polyphen		0.012	B
Vest4		0.053
MutPred		0.14		Loss of glycosylation at P30 (P = 0.0657)
MVP		0.32
MPC		0.43
ClinPred		0.27	T
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.078
gMVP		0.24
Mutation Taster		=86/14	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: rs2145484307; hg19: chr19-1250378;