rs534321202

Variant names:

• chr12-80209509-A-G
• rs534321202
• NM_001378609.3:c.78A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-80209509-A-G
• chr12-80209509-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001378609.3(OTOGL):​c.78A>G​(p.Gln26Gln) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.00000137 in 1,462,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: OTOGL NM_001378609.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.9807
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.66
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

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.78A>G	p.Gln26Gln	splice_region synonymous	Exon 2 of 59	NP_001365538.2	Q3ZCN5
	OTOGL	NM_001378610.3		c.78A>G	p.Gln26Gln	splice_region synonymous	Exon 5 of 62	NP_001365539.2	Q3ZCN5
	OTOGL	NM_173591.7		c.78A>G	p.Gln26Gln	splice_region synonymous	Exon 2 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.78A>G	p.Gln26Gln	splice_region synonymous	Exon 2 of 59	ENSP00000447211.2	Q3ZCN5
	OTOGL	ENST00000646859.1		c.78A>G	p.Gln26Gln	splice_region synonymous	Exon 7 of 63	ENSP00000496036.1	A0A2R8YF04
	OTOGL	ENST00000643417.1		n.738A>G		splice_region non_coding_transcript_exon	Exon 5 of 23

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152182 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 128962 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.63e-7 AC: 1 AN: 1310326 Hom.: 0 Cov.: 22 AF XY: 0.00000154 AC XY: 1 AN XY: 649452

African (AFR) AF: 0.00 AC: 0 AN: 29920

American (AMR) AF: 0.00 AC: 0 AN: 34210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24376

East Asian (EAS) AF: 0.00 AC: 0 AN: 35172

South Asian (SAS) AF: 0.00 AC: 0 AN: 75330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5536

European-Non Finnish (NFE) AF: 9.83e-7 AC: 1 AN: 1017270

Other (OTH) AF: 0.00 AC: 0 AN: 55378

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152182 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15268

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

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: 0.0000147 AC: 1 AN: 68022

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	-0.33
CADD	Benign	19
DANN	Benign	0.84
PhyloP100		4.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.98
dbscSNV1_RF	Pathogenic	0.87
SpliceAI score (max)		0.010		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: rs534321202; hg19: chr12-80603289;