Variant 12-102958346-GGCCGCAGCCGCGGCGGCCGCAGCC-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3BS2

The NM_004316.4(ASCL1):c.111_134del(p.Ala40_Ala47del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,435,264 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000065 ( 2 hom. )

Consequence

ASCL1
NM_004316.4 inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 2.34

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]

ASCL1 links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_004316.4

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASCL1	NM_004316.4 linkuse as main transcript	c.111_134del	p.Ala40_Ala47del	inframe_deletion	1/2	ENST00000266744.4
PAH	NM_001354304.2 linkuse as main transcript	c.-271_-248del		5_prime_UTR_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ASCL1	ENST00000266744.4 linkuse as main transcript	c.111_134del	p.Ala40_Ala47del	inframe_deletion	1/2	1	NM_004316.4	P1
PAH	ENST00000551337.5 linkuse as main transcript			5_prime_UTR_variant	1/5	3
PAH	ENST00000547319.1 linkuse as main transcript	n.41_64del		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes

AF:

0.0000400

AC:

AN:

150044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000499

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000662

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000248

AC:

AN:

64606

Hom.:

AF XY:

0.000289

AC XY:

AN XY:

38060

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000746

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000570

Gnomad OTH exome

AF:

0.000572

GnomAD4 exome

AF:

0.0000646

AC:

AN:

1285220

Hom.:

AF XY:

0.0000758

AC XY:

AN XY:

632884

show subpopulations

Gnomad4 AFR exome

AF:

0.000123

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000572

Gnomad4 OTH exome

AF:

0.000227

GnomAD4 genome

AF:

0.0000400

AC:

AN:

150044

Hom.:

Cov.:

AF XY:

0.0000546

AC XY:

AN XY:

73272

show subpopulations

Gnomad4 AFR

AF:

0.0000499

Gnomad4 AMR

AF:

0.0000662

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.000170

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Haddad syndrome

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Dec 01, 2003

- -

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.

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