dbSNP rs754558994: LEUTX:p.Ala131Glu (chr19-39785930-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001382345.1(LEUTX):c.392C>A(p.Ala131Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A131V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

LEUTX
NM_001382345.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.777

Publications

0 publications found

Variant links:

Genes affected

LEUTX (HGNC:31953): (leucine twenty homeobox) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LEUTX links:

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ACMG classification

Classification was made for transcript

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=0.08877334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LEUTX	NM_001382345.1 link	c.392C>A	p.Ala131Glu	missense_variant	Exon 3 of 3	ENST00000638280.2	NP_001369274.1
LEUTX	NM_001143832.2 link	c.302C>A	p.Ala101Glu	missense_variant	Exon 3 of 3		NP_001137304.1	A8MZ59-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LEUTX	ENST00000638280.2 link	c.392C>A	p.Ala131Glu	missense_variant	Exon 3 of 3	3	NM_001382345.1	ENSP00000491740.1		A8MZ59-2
LEUTX	ENST00000396841.4 link	c.302C>A	p.Ala101Glu	missense_variant	Exon 3 of 3	2		ENSP00000380053.3		A8MZ59-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1399418

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690218

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31598

American (AMR)

AF:

0.00

AC:

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.00

AC:

AN:

79236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078982

Other (OTH)

AF:

0.00

AC:

AN:

58008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.020

(source)

DANN

Benign

0.43

DEOGEN2

Benign

0.023

T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0043

M_CAP

Benign

0.010

MetaRNN

Benign

0.089

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

N;.

PhyloP100

-0.78

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.0

N;.

REVEL

Benign

0.17

Sift

Benign

0.040

D;.

Sift4G

Benign

0.13

T;.

Polyphen

0.20

B;.

Vest4

0.079

MutPred

0.34

Gain of solvent accessibility (P = 0.005);.;

MVP

0.19

ClinPred

0.096

GERP RS

-5.3

Varity_R

0.087

gMVP

0.038

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over