Variant 19-47414800-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001301059.2(MEIS3):c.514G>A(p.Asp172Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

MEIS3
NM_001301059.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.90

Variant links:

Genes affected

MEIS3 (HGNC:29537): (Meis homeobox 3) This gene encodes a homeobox protein and probable transcriptional regulator. The orthologous protein in mouse controls expression of 3-phosphoinositide dependent protein kinase 1, which promotes survival of pancreatic beta-cells. [provided by RefSeq, Sep 2016]

MEIS3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.825

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEIS3	NM_001301059.2 linkuse as main transcript	c.514G>A	p.Asp172Asn	missense_variant	6/13	ENST00000558555.6	NP_001287988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEIS3	ENST00000558555.6 linkuse as main transcript	c.514G>A	p.Asp172Asn	missense_variant	6/13	5	NM_001301059.2	ENSP00000454073	P1	Q99687-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250124

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135622

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461402

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726996

show subpopulations

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.514G>A (p.D172N) alteration is located in exon 6 (coding exon 6) of the MEIS3 gene. This alteration results from a G to A substitution at nucleotide position 514, causing the aspartic acid (D) at amino acid position 172 to be replaced by an asparagine (N). 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

0.69

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.27

.;.;.;.;.;T;.

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.93

D;D;D;D;.;D;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.82

D;D;D;D;D;D;D

MetaSVM

Pathogenic

0.98

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-4.8

D;D;.;D;D;D;D

REVEL

Pathogenic

0.92

Sift

Uncertain

0.0010

D;D;.;D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D;D;D;D

Polyphen

1.0

D;.;.;.;D;D;D

Vest4

0.85

MutPred

0.59

.;.;.;.;Loss of ubiquitination at K168 (P = 0.063);Loss of ubiquitination at K168 (P = 0.063);Loss of ubiquitination at K168 (P = 0.063);

MVP

0.97

MPC

0.73

ClinPred

0.99

GERP RS

3.8

Varity_R

0.80

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over