7-127611031-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001366110.1(PAX4):​c.*33A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,580,706 control chromosomes in the GnomAD database, including 222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 8 hom., cov: 33)
Exomes 𝑓: 0.016 ( 214 hom. )

Consequence

PAX4
NM_001366110.1 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.178
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 7-127611031-T-G is Benign according to our data. Variant chr7-127611031-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 358794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0106 (1612/152262) while in subpopulation NFE AF= 0.0166 (1130/68002). AF 95% confidence interval is 0.0158. There are 8 homozygotes in gnomad4. There are 797 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1612 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PAX4NM_001366110.1 linkuse as main transcriptc.*33A>C 3_prime_UTR_variant 12/12 ENST00000639438.3 NP_001353039.1
PAX4NM_001366111.1 linkuse as main transcriptc.914-46A>C intron_variant NP_001353040.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PAX4ENST00000639438.3 linkuse as main transcriptc.*33A>C 3_prime_UTR_variant 12/125 NM_001366110.1 ENSP00000491782 A2

Frequencies

GnomAD3 genomes
AF:
0.0106
AC:
1612
AN:
152144
Hom.:
8
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00328
Gnomad AMI
AF:
0.00329
Gnomad AMR
AF:
0.00281
Gnomad ASJ
AF:
0.00866
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.0238
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0166
Gnomad OTH
AF:
0.00623
GnomAD3 exomes
AF:
0.0103
AC:
2074
AN:
202238
Hom.:
20
AF XY:
0.0102
AC XY:
1102
AN XY:
108354
show subpopulations
Gnomad AFR exome
AF:
0.00215
Gnomad AMR exome
AF:
0.00155
Gnomad ASJ exome
AF:
0.00522
Gnomad EAS exome
AF:
0.0000640
Gnomad SAS exome
AF:
0.00275
Gnomad FIN exome
AF:
0.0217
Gnomad NFE exome
AF:
0.0169
Gnomad OTH exome
AF:
0.00888
GnomAD4 exome
AF:
0.0156
AC:
22323
AN:
1428444
Hom.:
214
Cov.:
56
AF XY:
0.0153
AC XY:
10806
AN XY:
707494
show subpopulations
Gnomad4 AFR exome
AF:
0.00226
Gnomad4 AMR exome
AF:
0.00176
Gnomad4 ASJ exome
AF:
0.00633
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00305
Gnomad4 FIN exome
AF:
0.0234
Gnomad4 NFE exome
AF:
0.0182
Gnomad4 OTH exome
AF:
0.0110
GnomAD4 genome
AF:
0.0106
AC:
1612
AN:
152262
Hom.:
8
Cov.:
33
AF XY:
0.0107
AC XY:
797
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.00327
Gnomad4 AMR
AF:
0.00274
Gnomad4 ASJ
AF:
0.00866
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000829
Gnomad4 FIN
AF:
0.0238
Gnomad4 NFE
AF:
0.0166
Gnomad4 OTH
AF:
0.00617
Alfa
AF:
0.0114
Hom.:
1
Bravo
AF:
0.00862
Asia WGS
AF:
0.00260
AC:
9
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingGeneDxAug 09, 2018- -
Maturity onset diabetes mellitus in young Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
2.3
DANN
Benign
0.57

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.

Other links and lift over

dbSNP: rs150578361; hg19: chr7-127251085; API