chr12-80211955-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001378609.3(OTOGL):​c.126G>A​(p.Gly42=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,571,058 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 (★).

Frequency

Genomes: 𝑓 0.00018 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

OTOGL
NM_001378609.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.490
Variant links:
Genes affected
OTOGL (HGNC:26901): (otogelin like) The protein encoded by this gene belongs to the otogelin family. This gene is expressed in the inner ear of vertebrates with the highest level of expression seen at the embryonic stage and lowest in adult. Knockdown studies in zebrafish suggest that this gene is essential for normal inner ear function. Mutations in this gene are associated with autosomal recessive deafness. [provided by RefSeq, Dec 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 12-80211955-G-A is Benign according to our data. Variant chr12-80211955-G-A is described in ClinVar as [Benign]. Clinvar id is 2890293.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.49 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OTOGLNM_001378609.3 linkuse as main transcriptc.126G>A p.Gly42= synonymous_variant 4/59 ENST00000547103.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OTOGLENST00000547103.7 linkuse as main transcriptc.126G>A p.Gly42= synonymous_variant 4/595 NM_001378609.3 P1
OTOGLENST00000646859.1 linkuse as main transcriptc.126G>A p.Gly42= synonymous_variant 9/63
OTOGLENST00000643417.1 linkuse as main transcriptn.786G>A non_coding_transcript_exon_variant 7/23

Frequencies

GnomAD3 genomes
AF:
0.000184
AC:
28
AN:
152136
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.0132
Gnomad AMR
AF:
0.0000656
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000831
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000188
AC:
36
AN:
191954
Hom.:
1
AF XY:
0.000251
AC XY:
26
AN XY:
103460
show subpopulations
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 SAS exome
AF:
0.000546
Gnomad FIN exome
AF:
0.000219
Gnomad NFE exome
AF:
0.000232
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000142
AC:
202
AN:
1418922
Hom.:
1
Cov.:
30
AF XY:
0.000146
AC XY:
103
AN XY:
703084
show subpopulations
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:
0.000416
Gnomad4 FIN exome
AF:
0.0000267
Gnomad4 NFE exome
AF:
0.000147
Gnomad4 OTH exome
AF:
0.000101
GnomAD4 genome
AF:
0.000184
AC:
28
AN:
152136
Hom.:
1
Cov.:
32
AF XY:
0.000188
AC XY:
14
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.0000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000831
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.000257

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeOct 17, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
CADD
Benign
7.8
DANN
Benign
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs375517066; hg19: chr12-80605735; API