Variant rs60083916 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_194248.3(OTOF):c.4799+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00385 in 1,613,758 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 44 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 52 hom. )

Consequence

OTOF
NM_194248.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.21

Variant links:

Genes affected

OTOF (HGNC:8515): (otoferlin) Mutations in this gene are a cause of neurosensory nonsyndromic recessive deafness, DFNB9. The short form of the encoded protein has 3 C2 domains, a single carboxy-terminal transmembrane domain found also in the C. elegans spermatogenesis factor FER-1 and human dysferlin, while the long form has 6 C2 domains. The homology suggests that this protein may be involved in vesicle membrane fusion. Several transcript variants encoding multiple isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OTOF links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 2-26465656-C-T is Benign according to our data. Variant chr2-26465656-C-T is described in ClinVar as [Benign]. Clinvar id is 263084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0148 (2253/152372) while in subpopulation AFR AF= 0.0477 (1985/41586). AF 95% confidence interval is 0.046. There are 44 homozygotes in gnomad4. There are 1072 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOF	NM_194248.3 linkuse as main transcript	c.4799+16G>A		intron_variant		ENST00000272371.7	NP_919224.1
OTOF	NM_194323.3 linkuse as main transcript	c.2498+16G>A		intron_variant		ENST00000339598.8	NP_919304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTOF	ENST00000272371.7 linkuse as main transcript	c.4799+16G>A		intron_variant		1	NM_194248.3	ENSP00000272371	A1	Q9HC10-1
OTOF	ENST00000339598.8 linkuse as main transcript	c.2498+16G>A		intron_variant		1	NM_194323.3	ENSP00000344521		Q9HC10-2

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2238

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0475

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00863

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00145

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00515

AC:

1295

AN:

251306

Hom.:

AF XY:

0.00428

AC XY:

582

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.0506

Gnomad AMR exome

AF:

0.00616

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00187

Gnomad OTH exome

AF:

0.00571

GnomAD4 exome

AF:

0.00271

AC:

3961

AN:

1461386

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

1854

AN XY:

727050

show subpopulations

Gnomad4 AFR exome

AF:

0.0518

Gnomad4 AMR exome

AF:

0.00655

Gnomad4 ASJ exome

AF:

0.000459

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00132

Gnomad4 OTH exome

AF:

0.00583

GnomAD4 genome

AF:

0.0148

AC:

2253

AN:

152372

Hom.:

Cov.:

AF XY:

0.0144

AC XY:

1072

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0477

Gnomad4 AMR

AF:

0.00862

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00144

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00807

Hom.:

Bravo

AF:

0.0169

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.34

DANN

Benign

0.76

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over