10-68231276-C-T

Variant names:

• chr10-68231276-C-T
• rs762047633
• NM_145178.4:c.402G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_145178.4(ATOH7):​c.402G>A​(p.Glu134Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ATOH7 NM_145178.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=1.06 with no splicing effect.

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.402G>A	p.Glu134Glu	synonymous	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.402G>A	p.Glu134Glu	synonymous	Exon 1 of 1	ENSP00000362777.3	Q8N100

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000415 AC: 1 AN: 240992 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000918

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455534 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724004

African (AFR) AF: 0.00 AC: 0 AN: 33146

American (AMR) AF: 0.00 AC: 0 AN: 44206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.00 AC: 0 AN: 39356

South Asian (SAS) AF: 0.00 AC: 0 AN: 85606

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5382

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110146

Other (OTH) AF: 0.00 AC: 0 AN: 60148

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		1.1

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

Other links and lift over

dbSNP: rs762047633; hg19: chr10-69991033;