Genetic Variant ATOH1:p.Pro50Pro (chr4-93829076-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_005172.2(ATOH1):c.150G>A(p.Pro50Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000423 in 1,613,748 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

ATOH1
NM_005172.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0900

Variant links:

Genes affected

ATOH1 (HGNC:797): (atonal bHLH transcription factor 1) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in neuron differentiation; positive regulation of neuron differentiation; and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including generation of neurons; inner ear morphogenesis; and positive regulation of inner ear auditory receptor cell differentiation. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ATOH1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 4-93829076-G-A is Benign according to our data. Variant chr4-93829076-G-A is described in ClinVar as [Benign]. Clinvar id is 3049113.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 364 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATOH1	NM_005172.2 link	c.150G>A	p.Pro50Pro	synonymous_variant	Exon 1 of 1	ENST00000306011.6	NP_005163.1	Q92858

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATOH1	ENST00000306011.6 link	c.150G>A	p.Pro50Pro	synonymous_variant	Exon 1 of 1	6	NM_005172.2	ENSP00000302216.4		Q92858

Frequencies

GnomAD3 genomes

AF:

0.00239

AC:

364

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

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:

0.0000294

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000516

AC:

129

AN:

249800

Hom.:

AF XY:

0.000362

AC XY:

AN XY:

135390

show subpopulations

Gnomad AFR exome

AF:

0.00716

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000218

AC:

319

AN:

1461560

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

128

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.00792

Gnomad4 AMR exome

AF:

0.000201

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.000629

GnomAD4 genome

AF:

0.00239

AC:

364

AN:

152188

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

162

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.00843

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.0000870

Hom.:

Bravo

AF:

0.00269

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ATOH1-related disorder

Benign:1

Dec 09, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.4

DANN

Benign

0.93

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

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