chr12-80233072-A-G

Variant names:

• chr12-80233072-A-G
• rs144176460
• NM_001378609.3:c.792A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001378609.3(OTOGL):​c.792A>G​(p.Gln264Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000815 in 1,595,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: OTOGL NM_001378609.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.264
• Publications: 0 publications found

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]

OTOGL Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 84B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-80233072-A-G is Benign according to our data. Variant chr12-80233072-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 504791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.264 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378609.3. 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
	OTOGL	NM_001378609.3	MANE Select	c.792A>G	p.Gln264Gln	synonymous	Exon 9 of 59	NP_001365538.2	Q3ZCN5
	OTOGL	NM_001378610.3		c.792A>G	p.Gln264Gln	synonymous	Exon 12 of 62	NP_001365539.2	Q3ZCN5
	OTOGL	NM_173591.7		c.792A>G	p.Gln264Gln	synonymous	Exon 9 of 59	NP_775862.4	Q3ZCN5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOGL	ENST00000547103.7	TSL:5 MANE Select	c.792A>G	p.Gln264Gln	synonymous	Exon 9 of 59	ENSP00000447211.2	Q3ZCN5
	OTOGL	ENST00000646859.1		c.792A>G	p.Gln264Gln	synonymous	Exon 14 of 63	ENSP00000496036.1	A0A2R8YF04
	OTOGL	ENST00000643417.1		n.1452A>G		non_coding_transcript_exon	Exon 12 of 23

Frequencies

GnomAD3 genomes AF: 0.000414 AC: 63 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.0000147

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000150 AC: 35 AN: 234060 AF XY: 0.000141

Gnomad AFR exome AF: 0.00172

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000275

Gnomad OTH exome AF: 0.000170

GnomAD4 exome AF: 0.0000464 AC: 67 AN: 1443562 Hom.: 0 Cov.: 31 AF XY: 0.0000431 AC XY: 31 AN XY: 718714

African (AFR) AF: 0.00126 AC: 42 AN: 33390

American (AMR) AF: 0.000112 AC: 5 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39094

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5754

European-Non Finnish (NFE) AF: 0.00000631 AC: 7 AN: 1108560

Other (OTH) AF: 0.000133 AC: 8 AN: 60158

GnomAD4 genome AF: 0.000414 AC: 63 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.000403 AC XY: 30 AN XY: 74468

African (AFR) AF: 0.00142 AC: 59 AN: 41582

American (AMR) AF: 0.000131 AC: 2 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000433 Hom.: 0

Bravo AF: 0.000484

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.58
DANN	Benign	0.33
PhyloP100		-0.26

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

Other links and lift over

dbSNP: rs144176460; hg19: chr12-80626852;