rs587777665

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Strong

The NM_145178.4(ATOH7):c.53delC(p.Pro18ArgfsTer69) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000317 in 1,165,920 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

ATOH7
NM_145178.4 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 0.531

Publications

3 publications found

Variant links:

Genes affected

ATOH7 (HGNC:13907): (atonal bHLH transcription factor 7) This intronless gene encodes a member of the basic helix-loop-helix family of transcription factors, with similarity to Drosophila atonal gene that controls photoreceptor development. Studies in mice suggest that this gene plays a central role in retinal ganglion cell and optic nerve formation. Mutations in this gene are associated with nonsyndromic congenital retinal nonattachment. [provided by RefSeq, Dec 2011]

ATOH7 Gene-Disease associations (from GenCC):

persistent hyperplastic primary vitreous, autosomal recessive
Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
persistent hyperplastic primary vitreous
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
anterior segment dysgenesis 7
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ATOH7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATOH7	NM_145178.4 link	c.53delC	p.Pro18ArgfsTer69	frameshift_variant	Exon 1 of 1	ENST00000373673.5	NP_660161.1	Q8N100F1T0H4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATOH7	ENST00000373673.5 link	c.53delC	p.Pro18ArgfsTer69	frameshift_variant	Exon 1 of 1	6	NM_145178.4	ENSP00000362777.3		Q8N100

Frequencies

GnomAD3 genomes

AF:

0.0000399

AC:

AN:

150284

Hom.:

Cov.:

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:

0.0000888

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

4282

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000305

AC:

AN:

1015636

Hom.:

Cov.:

AF XY:

0.0000334

AC XY:

AN XY:

478476

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20538

American (AMR)

AF:

0.00

AC:

AN:

6216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11378

East Asian (EAS)

AF:

0.00

AC:

AN:

20316

South Asian (SAS)

AF:

0.00

AC:

AN:

18924

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20024

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2584

European-Non Finnish (NFE)

AF:

0.0000354

AC:

AN:

876918

Other (OTH)

AF:

0.00

AC:

AN:

38738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000399

AC:

AN:

150284

Hom.:

Cov.:

AF XY:

0.0000682

AC XY:

AN XY:

73362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41190

American (AMR)

AF:

0.00

AC:

AN:

15086

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9686

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000888

AC:

AN:

67582

Other (OTH)

AF:

0.00

AC:

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Persistent hyperplastic primary vitreous, autosomal recessive

Pathogenic:1

Feb 15, 2012

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not provided

Uncertain:1

Aug 20, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change creates a premature translational stop signal (p.Pro18Argfs*69) in the ATOH7 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 135 amino acid(s) of the ATOH7 protein. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 144066). This premature translational stop signal has been observed in individual(s) with clinical features of persistent hyperplasia of the primary vitreous (PMID: 22068589). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs587777665, gnomAD 0.006%). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.53

Mutation Taster

=8/192

disease causing (ClinVar)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over