Variant 19-47414835-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001301059.2(MEIS3):c.479G>A(p.Arg160His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000262 in 1,412,208 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: 0.000026 ( 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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.901

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEIS3	NM_001301059.2 linkuse as main transcript	c.479G>A	p.Arg160His	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.479G>A	p.Arg160His	missense_variant	6/13	5	NM_001301059.2	ENSP00000454073	P1	Q99687-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

249598

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135406

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:

0.0000267

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000262

AC:

AN:

1412208

Hom.:

Cov.:

AF XY:

0.0000214

AC XY:

AN XY:

701798

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:

0.0000306

Gnomad4 OTH exome

AF:

0.0000526

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jun 22, 2023

The c.479G>A (p.R160H) 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 479, causing the arginine (R) at amino acid position 160 to be replaced by a histidine (H). 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

0.95

BayesDel_addAF

Uncertain

0.099

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.35

.;.;.;T;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

1.0

D;D;.;D;D

M_CAP

Benign

0.037

MetaRNN

Pathogenic

0.90

D;D;D;D;D

MetaSVM

Uncertain

-0.081

MutationAssessor

Uncertain

2.9

.;.;M;M;M

MutationTaster

Benign

1.0

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

PROVEAN

Pathogenic

-4.6

.;D;D;D;D

Sift

Pathogenic

0.0

.;D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D

Polyphen

1.0, 1.0

.;.;D;D;D

Vest4

0.94, 0.89, 0.95, 0.89

MutPred

0.76

.;.;Loss of solvent accessibility (P = 0.2034);Loss of solvent accessibility (P = 0.2034);Loss of solvent accessibility (P = 0.2034);

MVP

0.80

MPC

0.83

ClinPred

1.0

GERP RS

3.8

Varity_R

0.73

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

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

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