12-80211020-A-C

Position:

• chr12-80211020-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378609.3(OTOGL):​c.119+134A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00591 in 512,904 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (73 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (14 hom.)
• Consequence: OTOGL NM_001378609.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.286

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-80211020-A-C is Benign according to our data. Variant chr12-80211020-A-C is described in ClinVar as [Benign]. Clinvar id is 1267402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOGL	NM_001378609.3	c.119+134A>C		intron_variant		ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTOGL	ENST00000547103.7	c.119+134A>C		intron_variant		5	NM_001378609.3	ENSP00000447211.2
OTOGL	ENST00000646859.1	c.119+134A>C		intron_variant				ENSP00000496036.1
OTOGL	ENST00000643417.1	n.779+134A>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2380 AN: 152126 Hom.: 72 Cov.: 32

Gnomad AFR AF: 0.0544

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00629

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00862

GnomAD4 exome AF: 0.00181 AC: 651 AN: 360660 Hom.: 14 AF XY: 0.00163 AC XY: 298 AN XY: 182694

Gnomad4 AFR exome AF: 0.0517

Gnomad4 AMR exome AF: 0.00441

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000103

Gnomad4 FIN exome AF: 0.000320

Gnomad4 NFE exome AF: 0.000156

Gnomad4 OTH exome AF: 0.00536

GnomAD4 genome AF: 0.0156 AC: 2380 AN: 152244 Hom.: 73 Cov.: 32 AF XY: 0.0156 AC XY: 1165 AN XY: 74454

Gnomad4 AFR AF: 0.0543

Gnomad4 AMR AF: 0.00628

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00853

Alfa AF: 0.0108 Hom.: 3

Bravo AF: 0.0179

Asia WGS AF: 0.00406 AC: 14 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.35
DANN	Benign	0.62

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

Other links and lift over

dbSNP: rs17006505; hg19: chr12-80604800;