Genetic Variant NM_025245.3:c.79A>G (chr19-19618551-T-C) – 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_025245.3(PBX4):c.79A>G(p.Met27Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000154 in 1,299,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. M27L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

PBX4
NM_025245.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.26

Publications

0 publications found

Variant links:

Genes affected

PBX4 (HGNC:13403): (PBX homeobox 4) This gene encodes a member of the pre-B cell leukemia transcription factor family. These proteins are homeobox proteins that play critical roles in embryonic development and cellular differentiation both as Hox cofactors and through Hox-independent pathways. The encoded protein contains a homeobox DNA-binding domain, but specific functions of the protein have not been determined. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2011]

PBX4 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=0.18191198).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PBX4	NM_025245.3 link	c.79A>G	p.Met27Val	missense_variant	Exon 1 of 8	ENST00000251203.14	NP_079521.1	Q9BYU1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PBX4	ENST00000251203.14 link	c.79A>G	p.Met27Val	missense_variant	Exon 1 of 8	1	NM_025245.3	ENSP00000251203.5	Q9BYU1
PBX4	ENST00000557978.6 link	n.79A>G		non_coding_transcript_exon_variant	Exon 1 of 8	1		ENSP00000453348.1	H0YL59
PBX4	ENST00000558222.1 link	n.79A>G		non_coding_transcript_exon_variant	Exon 1 of 6	2		ENSP00000453069.1	H0YL59

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000154

AC:

AN:

1299460

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

643318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27020

American (AMR)

AF:

0.00

AC:

AN:

26128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21420

East Asian (EAS)

AF:

0.00

AC:

AN:

30666

South Asian (SAS)

AF:

0.0000156

AC:

AN:

64026

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46008

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3638

European-Non Finnish (NFE)

AF:

9.72e-7

AC:

AN:

1028448

Other (OTH)

AF:

0.00

AC:

AN:

52106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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

0.21

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.44

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.014

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

1.3

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.083

Sift

Benign

0.077

Sift4G

Benign

0.16

Polyphen

0.57

Vest4

0.24

MutPred

0.55

Loss of loop (P = 0.1258);

MVP

0.41

MPC

0.51

ClinPred

0.86

GERP RS

1.5

PromoterAI

-0.093

Neutral

(source)

Varity_R

0.28

gMVP

0.47

Mutation Taster

=89/11

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