7-127610572-C-T

Variant summary

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

The NM_001366110.1(PAX4):​c.*492G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 275,170 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 29 hom., cov: 31)
Exomes 𝑓: 0.010 ( 17 hom. )

Consequence

PAX4
NM_001366110.1 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

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]

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=-0.96).
BP6
Variant 7-127610572-C-T is Benign according to our data. Variant chr7-127610572-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 358784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0328 (2493/76080) while in subpopulation SAS AF= 0.0527 (127/2410). AF 95% confidence interval is 0.0479. There are 29 homozygotes in gnomad4. There are 1172 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 2493 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PAX4NM_001366110.1 linkuse as main transcriptc.*492G>A 3_prime_UTR_variant 12/12 ENST00000639438.3 NP_001353039.1
PAX4NM_001366111.1 linkuse as main transcriptc.*280G>A 3_prime_UTR_variant 10/10 NP_001353040.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PAX4ENST00000639438.3 linkuse as main transcriptc.*492G>A 3_prime_UTR_variant 12/125 NM_001366110.1 ENSP00000491782 A2
PAX4ENST00000341640.6 linkuse as main transcriptc.*492G>A 3_prime_UTR_variant 9/91 ENSP00000339906 O43316-4

Frequencies

GnomAD3 genomes
AF:
0.0327
AC:
2487
AN:
76024
Hom.:
29
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0505
Gnomad AMI
AF:
0.0864
Gnomad AMR
AF:
0.0204
Gnomad ASJ
AF:
0.0169
Gnomad EAS
AF:
0.00520
Gnomad SAS
AF:
0.0532
Gnomad FIN
AF:
0.0221
Gnomad MID
AF:
0.0462
Gnomad NFE
AF:
0.0304
Gnomad OTH
AF:
0.0288
GnomAD4 exome
AF:
0.0101
AC:
2012
AN:
199090
Hom.:
17
Cov.:
0
AF XY:
0.0106
AC XY:
1123
AN XY:
105922
show subpopulations
Gnomad4 AFR exome
AF:
0.0172
Gnomad4 AMR exome
AF:
0.00482
Gnomad4 ASJ exome
AF:
0.00682
Gnomad4 EAS exome
AF:
0.00214
Gnomad4 SAS exome
AF:
0.0164
Gnomad4 FIN exome
AF:
0.00795
Gnomad4 NFE exome
AF:
0.00990
Gnomad4 OTH exome
AF:
0.00917
GnomAD4 genome
AF:
0.0328
AC:
2493
AN:
76080
Hom.:
29
Cov.:
31
AF XY:
0.0316
AC XY:
1172
AN XY:
37136
show subpopulations
Gnomad4 AFR
AF:
0.0507
Gnomad4 AMR
AF:
0.0204
Gnomad4 ASJ
AF:
0.0169
Gnomad4 EAS
AF:
0.00521
Gnomad4 SAS
AF:
0.0527
Gnomad4 FIN
AF:
0.0221
Gnomad4 NFE
AF:
0.0304
Gnomad4 OTH
AF:
0.0303

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

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

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.96
CADD
Benign
0.39
DANN
Benign
0.47

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: rs405576; hg19: chr7-127250626; COSMIC: COSV58389037; COSMIC: COSV58389037; API