rs405576

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001366110.1(PAX4):​c.*492G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 199,554 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.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

PAX4
NM_001366110.1 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.29
Variant links:
Genes affected
PAX4 (HGNC:8618): (paired box 4) This gene is a member of the paired box (PAX) family of transcription factors. Members of this gene family typically contain a paired box domain, an octapeptide, and a paired-type homeodomain. These genes play critical roles during fetal development and cancer growth. The paired box 4 gene is involved in pancreatic islet development and mouse studies have demonstrated a role for this gene in differentiation of insulin-producing beta cells. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PAX4NM_001366110.1 linkc.*492G>T 3_prime_UTR_variant Exon 12 of 12 ENST00000639438.3 NP_001353039.1
PAX4NM_001366111.1 linkc.*280G>T 3_prime_UTR_variant Exon 10 of 10 NP_001353040.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PAX4ENST00000639438 linkc.*492G>T 3_prime_UTR_variant Exon 12 of 12 5 NM_001366110.1 ENSP00000491782.1 A0A1W2PPX4
PAX4ENST00000341640 linkc.*492G>T 3_prime_UTR_variant Exon 9 of 9 1 ENSP00000339906.2 O43316-4
PAX4ENST00000378740.6 linkc.*280G>T downstream_gene_variant 1 ENSP00000368014.4 J3KPG0

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.0000100
AC:
2
AN:
199554
Hom.:
0
Cov.:
0
AF XY:
0.00000942
AC XY:
1
AN XY:
106164
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:
0.0000167
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
0.13
DANN
Benign
0.46

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: chr7-127250626; API