NM_001378609.3:c.3729G>C

Variant names:

• chr12-80318640-G-C
• rs10778725
• NM_001378609.3:c.3729G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001378609.3(OTOGL):​c.3729G>C​(p.Pro1243Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P1243P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OTOGL NM_001378609.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525
• Publications: 17 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=0.525 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.3729G>C	p.Pro1243Pro	synonymous	Exon 33 of 59	NP_001365538.2	Q3ZCN5
	OTOGL	NM_001378610.3		c.3729G>C	p.Pro1243Pro	synonymous	Exon 36 of 62	NP_001365539.2	Q3ZCN5
	OTOGL	NM_173591.7		c.3729G>C	p.Pro1243Pro	synonymous	Exon 33 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.3729G>C	p.Pro1243Pro	synonymous	Exon 33 of 59	ENSP00000447211.2	Q3ZCN5
	OTOGL	ENST00000646859.1		c.3594G>C	p.Pro1198Pro	synonymous	Exon 37 of 63	ENSP00000496036.1	A0A2R8YF04

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152110 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1317298 Hom.: 0 Cov.: 43 AF XY: 0.00 AC XY: 0 AN XY: 648466

African (AFR) AF: 0.00 AC: 0 AN: 27152

American (AMR) AF: 0.00 AC: 0 AN: 24060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22754

East Asian (EAS) AF: 0.00 AC: 0 AN: 31718

South Asian (SAS) AF: 0.00 AC: 0 AN: 64264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5364

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1041034

Other (OTH) AF: 0.00 AC: 0 AN: 53988

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152110 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74292

African (AFR) AF: 0.00 AC: 0 AN: 41410

American (AMR) AF: 0.00 AC: 0 AN: 15256

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2094

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.8
DANN	Benign	0.59
PhyloP100		0.53

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: rs10778725; hg19: chr12-80712420;