Variant 7-127611677-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 5P and 4B. PVS1_StrongPP5BS2

The NM_001366110.1(PAX4):c.772-1G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000436 in 1,605,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

PAX4
NM_001366110.1 splice_acceptor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 0.828

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]

PAX4 links:

PAX4 (HGNC:):

PAX4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.13352273 fraction of the gene. Cryptic splice site detected, with MaxEntScore 9.8, offset of 3, new splice context is: ttgctttttttttttaacAGtcc. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

PP5

Variant 7-127611677-C-T is Pathogenic according to our data. Variant chr7-127611677-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 13794.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-127611677-C-T is described in Lovd as [Likely_pathogenic].

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAX4	NM_001366110.1 linkuse as main transcript	c.772-1G>A		splice_acceptor_variant, intron_variant		ENST00000639438.3	NP_001353039.1
PAX4	NM_001366111.1 linkuse as main transcript	c.772-1G>A		splice_acceptor_variant, intron_variant			NP_001353040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAX4	ENST00000639438.3 linkuse as main transcript	c.772-1G>A		splice_acceptor_variant, intron_variant		5	NM_001366110.1	ENSP00000491782.1		A0A1W2PPX4

Frequencies

GnomAD3 genomes

AF:

0.00000666

AC:

AN:

150170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000247

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000410

AC:

AN:

243764

Hom.:

AF XY:

0.00000754

AC XY:

AN XY:

132628

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000552

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1455580

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000666

AC:

AN:

150170

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73206

show subpopulations

Gnomad4 AFR

AF:

0.0000247

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Maturity-onset diabetes of the young type 9

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 01, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

0.00011

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

0.98

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Benign

0.64

GERP RS

4.5

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.77

SpliceAI score (max)

0.65

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.34

Position offset: -4

DS_AL_spliceai

0.65

Position offset: -1

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