chr4-93829213-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005172.2(ATOH1):​c.287G>T​(p.Arg96Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ATOH1
NM_005172.2 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.773
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13755795).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATOH1NM_005172.2 linkc.287G>T p.Arg96Leu missense_variant Exon 1 of 1 ENST00000306011.6 NP_005163.1 Q92858

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATOH1ENST00000306011.6 linkc.287G>T p.Arg96Leu missense_variant Exon 1 of 1 6 NM_005172.2 ENSP00000302216.4 Q92858

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1431666
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
708560
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
ESP6500AA
AF:
0.000229
AC:
1
ESP6500EA
AF:
0.00
AC:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 01, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.287G>T (p.R96L) alteration is located in exon 1 (coding exon 1) of the ATOH1 gene. This alteration results from a G to T substitution at nucleotide position 287, causing the arginine (R) at amino acid position 96 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Uncertain
0.044
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.23
T
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.35
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.58
T
M_CAP
Uncertain
0.15
D
MetaRNN
Benign
0.14
T
MetaSVM
Uncertain
0.048
D
MutationAssessor
Benign
0.0
N
PrimateAI
Pathogenic
0.79
T
PROVEAN
Benign
-0.74
N
REVEL
Benign
0.25
Sift
Benign
0.073
T
Sift4G
Benign
0.21
T
Polyphen
0.20
B
Vest4
0.098
MVP
0.61
MPC
0.76
ClinPred
0.10
T
GERP RS
2.3
Varity_R
0.095
gMVP
0.29

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.

Other links and lift over

dbSNP: rs368475681; hg19: chr4-94750364; API