rs144912719

Variant names:

• chr16-21678452-G-GTA
• rs144912719
• NM_144672.4:c.-4-58_-4-57insAT

Your query was ambiguous. Multiple possible variants found:

• chr16-21678452-G-GTA
• chr16-21678452-G-GTATA
• chr16-21678452-G-GTATATA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_144672.4(OTOA):​c.-4-58_-4-57insAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 984,452 control chromosomes in the GnomAD database, including 688 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.049 (443 hom., cov: 30)
  • Exomes 𝑓: 0.017 (245 hom.)
• Consequence: OTOA NM_144672.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.214
• Publications: 2 publications found

Genes affected

OTOA (HGNC:16378): (otoancorin) The protein encoded by this gene is specifically expressed in the inner ear, and is located at the interface between the apical surface of the inner ear sensory epithelia and their overlying acellular gels. It is prposed that this protein is involved in the attachment of the inner ear acellular gels to the apical surface of the underlying nonsensory cells. Mutations in this gene are associated with autosomal recessive deafness type 22 (DFNB22). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

OTOA Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 22

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae)
• 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 -10 ACMG points.

• BP6: Variant 16-21678452-G-GTA is Benign according to our data. Variant chr16-21678452-G-GTA is described in ClinVar as Benign. ClinVar VariationId is 1236082.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144672.4. 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
	OTOA	NM_144672.4	MANE Select	c.-4-58_-4-57insAT		intron	N/A	NP_653273.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOA	ENST00000646100.2	MANE Select	c.-4-59_-4-58insTA		intron	N/A	ENSP00000496564.2	Q7RTW8-5
	OTOA	ENST00000647277.1		n.-4-59_-4-58insTA		intron	N/A	ENSP00000495594.1	A0A2R8YG28
	OTOA	ENST00000388958.8	TSL:1	c.-63_-62insTA		upstream_gene	N/A	ENSP00000373610.3	Q7RTW8-5

Frequencies

GnomAD3 genomes AF: 0.0489 AC: 7379 AN: 150986 Hom.: 440 Cov.: 30

Gnomad AFR AF: 0.0777

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0326

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.0492

Gnomad FIN AF: 0.00932

Gnomad MID AF: 0.0192

Gnomad NFE AF: 0.00933

Gnomad OTH AF: 0.0553

GnomAD4 exome AF: 0.0174 AC: 14496 AN: 833390 Hom.: 245 AF XY: 0.0176 AC XY: 7606 AN XY: 433094

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0371 AC: 710 AN: 19154

American (AMR) AF: 0.100 AC: 3092 AN: 30858

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 347 AN: 21196

East Asian (EAS) AF: 0.201 AC: 5316 AN: 26432

South Asian (SAS) AF: 0.0196 AC: 1308 AN: 66626

European-Finnish (FIN) AF: 0.00777 AC: 364 AN: 46838

Middle Eastern (MID) AF: 0.0169 AC: 49 AN: 2904

European-Non Finnish (NFE) AF: 0.00436 AC: 2532 AN: 580818

Other (OTH) AF: 0.0202 AC: 778 AN: 38564

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0489 AC: 7386 AN: 151062 Hom.: 443 Cov.: 30 AF XY: 0.0508 AC XY: 3749 AN XY: 73744

African (AFR) AF: 0.0778 AC: 3194 AN: 41072

American (AMR) AF: 0.111 AC: 1670 AN: 15024

Ashkenazi Jewish (ASJ) AF: 0.0326 AC: 113 AN: 3466

East Asian (EAS) AF: 0.259 AC: 1321 AN: 5094

South Asian (SAS) AF: 0.0487 AC: 233 AN: 4782

European-Finnish (FIN) AF: 0.00932 AC: 97 AN: 10408

Middle Eastern (MID) AF: 0.0175 AC: 5 AN: 286

European-Non Finnish (NFE) AF: 0.00932 AC: 633 AN: 67918

Other (OTH) AF: 0.0538 AC: 113 AN: 2100

Alfa AF: 0.00409 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.21

Splicing

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

Other links and lift over

dbSNP: rs144912719; hg19: chr16-21689773;