NM_145178.4:c.396G>C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 5P and 4B. PM1PM2PP2BP4_Strong

The NM_145178.4(ATOH7):c.396G>C(p.Glu132Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E132E) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ATOH7
NM_145178.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.157

Publications

0 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: Unknown, AR 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 1 ACMG points.

PM1

In a chain Transcription factor ATOH7 (size 151) in uniprot entity ATOH7_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_145178.4

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 4 curated pathogenic missense variants (we use a threshold of 10). The gene has 1 curated benign missense variants. Gene score misZ: 0.30531 (below the threshold of 3.09). Trascript score misZ: -1.2226 (below the threshold of 3.09). GenCC associations: The gene is linked to persistent hyperplastic primary vitreous, autosomal recessive, persistent hyperplastic primary vitreous, anterior segment dysgenesis 7.

BP4

Computational evidence support a benign effect (MetaRNN=0.05023539).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145178.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATOH7	NM_145178.4	MANE Select	c.396G>C	p.Glu132Asp	missense	Exon 1 of 1	NP_660161.1	Q8N100

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATOH7	ENST00000373673.5	TSL:6 MANE Select	c.396G>C	p.Glu132Asp	missense	Exon 1 of 1	ENSP00000362777.3	Q8N100

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1456904

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724682

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33204

American (AMR)

AF:

0.00

AC:

AN:

44290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26038

East Asian (EAS)

AF:

0.00

AC:

AN:

39376

South Asian (SAS)

AF:

0.00

AC:

AN:

85692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52088

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5520

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1110506

Other (OTH)

AF:

0.00

AC:

AN:

60190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.592

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.041

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.44

M_CAP

Benign

0.037

MetaRNN

Benign

0.050

MetaSVM

Uncertain

-0.21

MutationAssessor

Benign

0.20

PhyloP100

0.16

PrimateAI

Benign

0.43

PROVEAN

Benign

0.32

REVEL

Benign

0.23

Sift

Benign

0.78

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.048

MutPred

0.22

Loss of methylation at K128 (P = 0.0562)

MVP

0.52

MPC

0.73

ClinPred

0.029

GERP RS

2.2

Varity_R

0.056

gMVP

0.30

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over