rs10506821

Variant names:

• chr12-80103143-C-A
• rs10506821
• NM_001378609.3:c.-20+3538C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-80103143-C-A
• chr12-80103143-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001378609.3(OTOGL):​c.-20+3538C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OTOGL NM_001378609.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.13
• Publications: 7 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

ENSG00000230291 (HGNC:):

RPL26P32 (HGNC:36448):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOGL	NM_001378609.3	c.-20+3538C>A		intron_variant	Intron 1 of 58	ENST00000547103.7	NP_001365538.2
RPL26P32		n.80103143C>A		intragenic_variant
OTOGL	NM_001378610.3	c.-592+3538C>A		intron_variant	Intron 1 of 61		NP_001365539.2
OTOGL	NM_001368062.3	c.-1032+3538C>A		intron_variant	Intron 1 of 62		NP_001354991.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOGL	ENST00000547103.7	c.-20+3538C>A		intron_variant	Intron 1 of 58	5	NM_001378609.3	ENSP00000447211.2
ENSG00000230291	ENST00000492623.1	n.191G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
OTOGL	ENST00000646859.1	c.-1032+3538C>A		intron_variant	Intron 1 of 62			ENSP00000496036.1
OTOGL	ENST00000643417.1	n.69+3538C>A		intron_variant	Intron 1 of 22

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1028268 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 531158

African (AFR) AF: 0.00 AC: 0 AN: 26252

American (AMR) AF: 0.00 AC: 0 AN: 44150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23536

East Asian (EAS) AF: 0.00 AC: 0 AN: 37616

South Asian (SAS) AF: 0.00 AC: 0 AN: 77228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4702

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 721578

Other (OTH) AF: 0.00 AC: 0 AN: 46170

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	1.7
DANN	Benign	0.60
PhyloP100		3.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10506821; hg19: chr12-80496923;