12-102958393-CGCAGCAGCAGCAGCAGCAGCAGCAGCA-CGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004316.4(ASCL1):​c.157_186dupCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG​(p.Gln53_Gln62dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000017 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ASCL1
NM_004316.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.219
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 21 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ASCL1NM_004316.4 linkuse as main transcriptc.157_186dupCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG p.Gln53_Gln62dup conservative_inframe_insertion 1/2 ENST00000266744.4 NP_004307.2 P50553
PAHNM_001354304.2 linkuse as main transcriptc.-324_-295dupTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC 5_prime_UTR_variant 1/14 NP_001341233.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ASCL1ENST00000266744.4 linkuse as main transcriptc.157_186dupCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG p.Gln53_Gln62dup conservative_inframe_insertion 1/21 NM_004316.4 ENSP00000266744.3 P50553
PAHENST00000547319.1 linkuse as main transcriptn.-13_17dupTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC non_coding_transcript_exon_variant 1/34
PAHENST00000551337.5 linkuse as main transcriptc.-324_-295dupTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC upstream_gene_variant 3 ENSP00000447620.1 F8W0A0

Frequencies

GnomAD3 genomes
AF:
0.000140
AC:
21
AN:
150120
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.000367
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000132
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000197
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000445
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000169
AC:
23
AN:
1356952
Hom.:
0
Cov.:
17
AF XY:
0.0000209
AC XY:
14
AN XY:
669242
show subpopulations
Gnomad4 AFR exome
AF:
0.000175
Gnomad4 AMR exome
AF:
0.000119
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000180
Gnomad4 SAS exome
AF:
0.0000263
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000378
Gnomad4 OTH exome
AF:
0.0000354
GnomAD4 genome
AF:
0.000140
AC:
21
AN:
150120
Hom.:
0
Cov.:
0
AF XY:
0.000164
AC XY:
12
AN XY:
73222
show subpopulations
Gnomad4 AFR
AF:
0.000367
Gnomad4 AMR
AF:
0.000132
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000197
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000445
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs3832799; hg19: chr12-103352171; API