19-1250309-C-T

Variant names:

• chr19-1250309-C-T
• rs971142541
• NM_001388306.1:c.13C>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.13C>T​(p.Pro5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 989,356 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts 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. P5A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: MIDN NM_001388306.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58
• 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=0.24691275).

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.13C>T	p.Pro5Ser	missense	Exon 2 of 9	NP_001375235.1	A0A804HKJ8
	MIDN	NM_001388474.1		c.13C>T	p.Pro5Ser	missense	Exon 1 of 7	NP_001375403.1	Q504T8
	MIDN	NM_177401.5		c.13C>T	p.Pro5Ser	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.13C>T	p.Pro5Ser	missense	Exon 2 of 9	ENSP00000507955.1	A0A804HKJ8
	MIDN	ENST00000591446.7	TSL:1	c.13C>T	p.Pro5Ser	missense	Exon 1 of 7	ENSP00000467679.1	Q504T8
	MIDN	ENST00000937331.1		c.13C>T	p.Pro5Ser	missense	Exon 2 of 9	ENSP00000607390.1

Frequencies

GnomAD3 genomes AF: 0.0000204 AC: 3 AN: 146732 Hom.: 1 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: 0.0000454

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000154 AC: 13 AN: 842624 Hom.: 0 Cov.: 29 AF XY: 0.0000154 AC XY: 6 AN XY: 390072

African (AFR) AF: 0.00 AC: 0 AN: 15916

American (AMR) AF: 0.00 AC: 0 AN: 1316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5370

East Asian (EAS) AF: 0.00 AC: 0 AN: 4040

South Asian (SAS) AF: 0.00 AC: 0 AN: 17206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1644

European-Non Finnish (NFE) AF: 0.0000169 AC: 13 AN: 767770

Other (OTH) AF: 0.00 AC: 0 AN: 27826

GnomAD4 genome AF: 0.0000204 AC: 3 AN: 146732 Hom.: 1 Cov.: 32 AF XY: 0.0000420 AC XY: 3 AN XY: 71388

African (AFR) AF: 0.00 AC: 0 AN: 40808

American (AMR) AF: 0.00 AC: 0 AN: 14800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3398

East Asian (EAS) AF: 0.00 AC: 0 AN: 5064

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000454 AC: 3 AN: 66014

Other (OTH) AF: 0.00 AC: 0 AN: 2028

Alfa AF: 0.00 Hom.: 0

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	0.083
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.91	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.6
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.093
MutPred		0.13		Gain of MoRF binding (P = 0.0144)
MVP		0.47
MPC		0.30
ClinPred		0.39	T
GERP RS		2.6
PromoterAI		-0.064	Neutral
Varity_R		0.16
gMVP		0.55
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: rs971142541; hg19: chr19-1250308;