GeneBe

rs3832799

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004316.4(ASCL1):​c.160_186delCAGCAGCAGCAGCAGCAGCAGCAGCAG​(p.Gln54_Gln62del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,507,072 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0000088 ( 0 hom. )

Consequence

ASCL1
NM_004316.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.809

Publications

15 publications found
Variant links:
Genes affected
ASCL1 (HGNC:738): (achaete-scute family bHLH transcription factor 1) This gene encodes a member of the basic helix-loop-helix (BHLH) family of transcription factors. The protein activates transcription by binding to the E box (5'-CANNTG-3'). Dimerization with other BHLH proteins is required for efficient DNA binding. This protein plays a role in the neuronal commitment and differentiation and in the generation of olfactory and autonomic neurons. Mutations in this gene may contribute to the congenital central hypoventilation syndrome (CCHS) phenotype in rare cases. [provided by RefSeq, Jul 2008]
PAH (HGNC:8582): (phenylalanine hydroxylase) This gene encodes a member of the biopterin-dependent aromatic amino acid hydroxylase protein family. The encoded phenylalanine hydroxylase enzyme hydroxylates phenylalanine to tyrosine and is the rate-limiting step in phenylalanine catabolism. Deficiency of this enzyme activity results in the autosomal recessive disorder phenylketonuria. [provided by RefSeq, Aug 2017]
PAH Gene-Disease associations (from GenCC):
  • phenylketonuria
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Myriad Women’s Health
  • classic phenylketonuria
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • maternal phenylketonuria
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • mild hyperphenylalaninemia
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • mild phenylketonuria
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • tetrahydrobiopterin-responsive hyperphenylalaninemia/phenylketonuria
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASCL1NM_004316.4 linkc.160_186delCAGCAGCAGCAGCAGCAGCAGCAGCAG p.Gln54_Gln62del conservative_inframe_deletion Exon 1 of 2 ENST00000266744.4 NP_004307.2 P50553
PAH n.102958420_102958394delTGCTGCTGCTGCTGCTGCTGCTGCTGC bidirectional_gene_fusion
PAHNM_001354304.2 linkc.-321_-295delTGCTGCTGCTGCTGCTGCTGCTGCTGC 5_prime_UTR_variant Exon 1 of 14 NP_001341233.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ASCL1ENST00000266744.4 linkc.160_186delCAGCAGCAGCAGCAGCAGCAGCAGCAG p.Gln54_Gln62del conservative_inframe_deletion Exon 1 of 2 1 NM_004316.4 ENSP00000266744.3 P50553

Frequencies

GnomAD3 genomes
AF:
0.0000133
AC:
2
AN:
150120
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000297
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000884
AC:
12
AN:
1356952
Hom.:
0
AF XY:
0.0000120
AC XY:
8
AN XY:
669242
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
28512
American (AMR)
AF:
0.00
AC:
0
AN:
33690
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24016
East Asian (EAS)
AF:
0.00
AC:
0
AN:
33382
South Asian (SAS)
AF:
0.00
AC:
0
AN:
75998
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
41214
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4084
European-Non Finnish (NFE)
AF:
0.0000113
AC:
12
AN:
1059588
Other (OTH)
AF:
0.00
AC:
0
AN:
56468
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.442
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000133
AC:
2
AN:
150120
Hom.:
0
Cov.:
0
AF XY:
0.0000137
AC XY:
1
AN XY:
73222
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
40886
American (AMR)
AF:
0.00
AC:
0
AN:
15138
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3456
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5070
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4768
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10154
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
312
European-Non Finnish (NFE)
AF:
0.0000297
AC:
2
AN:
67382
Other (OTH)
AF:
0.00
AC:
0
AN:
2052
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.81
Mutation Taster
=157/43
disease causing (fs/PTC)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs3832799; hg19: chr12-103352171; API