19-1251864-C-T

Variant names:

• chr19-1251864-C-T
• NM_001388306.1:c.347C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001388306.1(MIDN):​c.347C>T​(p.Ser116Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,224 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MIDN NM_001388306.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.99

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4166599).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIDN	NM_001388306.1	c.347C>T	p.Ser116Phe	missense_variant	Exon 4 of 9	ENST00000682408.1	NP_001375235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIDN	ENST00000682408.1	c.347C>T	p.Ser116Phe	missense_variant	Exon 4 of 9		NM_001388306.1	ENSP00000507955.1
MIDN	ENST00000591446.7	c.347C>T	p.Ser116Phe	missense_variant	Exon 3 of 7	1		ENSP00000467679.1
MIDN	ENST00000300952.7	c.347C>T	p.Ser116Phe	missense_variant	Exon 4 of 8	5		ENSP00000300952.2
MIDN	ENST00000591302.1	n.415C>T		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461224 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726896

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.347C>T (p.S116F) alteration is located in exon 4 (coding exon 3) of the MIDN gene. This alteration results from a C to T substitution at nucleotide position 347, causing the serine (S) at amino acid position 116 to be replaced by a phenylalanine (F). 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	1.0
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.70	.;D;D
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D;D;.
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	1.7	.;L;L
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.5	.;D;.
REVEL	Benign	0.25
Sift	Uncertain	0.0010	.;D;.
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.90, 0.90
MutPred		0.25		Loss of disorder (P = 0.0134);Loss of disorder (P = 0.0134);Loss of disorder (P = 0.0134);
MVP		0.63
MPC		0.92
ClinPred		0.99	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.62
gMVP		0.68

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-1251863;