rs536538111

Variant names:

• chr12-80336990-C-A
• rs536538111
• NM_001378609.3:c.4846C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-80336990-C-A
• chr12-80336990-C-G
• chr12-80336990-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_001378609.3(OTOGL):​c.4846C>A​(p.Arg1616Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000042 in 1,428,240 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 (★). Synonymous variant affecting the same amino acid position (i.e. R1616R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: OTOGL NM_001378609.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.97
• Publications: 2 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: Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.12).
• BP6: Variant 12-80336990-C-A is Benign according to our data. Variant chr12-80336990-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 227823.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOGL	NM_001378609.3	MANE Select	c.4846C>A	p.Arg1616Arg	synonymous	Exon 42 of 59	NP_001365538.2
	OTOGL	NM_001378610.3		c.4846C>A	p.Arg1616Arg	synonymous	Exon 45 of 62	NP_001365539.2
	OTOGL	NM_173591.7		c.4846C>A	p.Arg1616Arg	synonymous	Exon 42 of 59	NP_775862.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOGL	ENST00000547103.7	TSL:5 MANE Select	c.4846C>A	p.Arg1616Arg	synonymous	Exon 42 of 59	ENSP00000447211.2
	OTOGL	ENST00000646859.1		c.4711C>A	p.Arg1571Arg	synonymous	Exon 46 of 63	ENSP00000496036.1
	OTOGL	ENST00000298820.7	TSL:5	c.145C>A	p.Arg49Arg	synonymous	Exon 3 of 18	ENSP00000298820.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000101 AC: 2 AN: 198178 AF XY: 0.00000944

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: 0.0000514

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000420 AC: 6 AN: 1428240 Hom.: 0 Cov.: 32 AF XY: 0.00000848 AC XY: 6 AN XY: 707470

African (AFR) AF: 0.00 AC: 0 AN: 32754

American (AMR) AF: 0.00 AC: 0 AN: 40930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25460

East Asian (EAS) AF: 0.00 AC: 0 AN: 38690

South Asian (SAS) AF: 0.0000492 AC: 4 AN: 81316

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51770

Middle Eastern (MID) AF: 0.000351 AC: 2 AN: 5706

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092484

Other (OTH) AF: 0.00 AC: 0 AN: 59130

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.12
CADD	Benign	9.1
DANN	Benign	0.67
PhyloP100		4.0
PromoterAI		-0.038	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs536538111; hg19: chr12-80730770;