Variant 3-46701259-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001370524.1(TMIE):c.-66-4531A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 361,318 control chromosomes in the GnomAD database, including 12,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3913 hom., cov: 31)

Exomes 𝑓: 0.30 ( 8935 hom. )

Consequence

TMIE
NM_001370524.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.38

Variant links:

Genes affected

TMIE (HGNC:30800): (transmembrane inner ear) This gene encodes a transmembrane inner ear protein. Studies in mouse suggest that this gene is required for normal postnatal maturation of sensory hair cells in the cochlea, including correct development of stereocilia bundles. This gene is one of multiple genes responsible for recessive non-syndromic deafness (DFNB), also known as autosomal recessive nonsyndromic hearing loss (ARNSHL), the most common form of congenitally acquired inherited hearing impairment. [provided by RefSeq, Mar 2009]

TMIE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 3-46701259-A-T is Benign according to our data. Variant chr3-46701259-A-T is described in ClinVar as [Benign]. Clinvar id is 1272920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMIE	NM_001370524.1 linkuse as main transcript	c.-66-4531A>T		intron_variant			NP_001357453.1
TMIE	NM_001370525.1 linkuse as main transcript	c.-66-4531A>T		intron_variant			NP_001357454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMIE	ENST00000644830.1 linkuse as main transcript	c.-66-4531A>T		intron_variant				ENSP00000495111

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32138

AN:

150788

Hom.:

3908

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0878

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.252

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.262

Gnomad FIN

AF:

0.251

Gnomad MID

AF:

0.224

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.225

GnomAD4 exome

AF:

0.302

AC:

63491

AN:

210426

Hom.:

8935

AF XY:

0.301

AC XY:

33666

AN XY:

111900

show subpopulations

Gnomad4 AFR exome

AF:

0.122

Gnomad4 AMR exome

AF:

0.327

Gnomad4 ASJ exome

AF:

0.282

Gnomad4 EAS exome

AF:

0.311

Gnomad4 SAS exome

AF:

0.263

Gnomad4 FIN exome

AF:

0.278

Gnomad4 NFE exome

AF:

0.316

Gnomad4 OTH exome

AF:

0.294

GnomAD4 genome

AF:

0.213

AC:

32146

AN:

150892

Hom.:

3913

Cov.:

AF XY:

0.214

AC XY:

15756

AN XY:

73784

show subpopulations

Gnomad4 AFR

AF:

0.0876

Gnomad4 AMR

AF:

0.252

Gnomad4 ASJ

AF:

0.223

Gnomad4 EAS

AF:

0.220

Gnomad4 SAS

AF:

0.263

Gnomad4 FIN

AF:

0.251

Gnomad4 NFE

AF:

0.270

Gnomad4 OTH

AF:

0.222

Alfa

AF:

0.116

Hom.:

191

Bravo

AF:

0.205

Asia WGS

AF:

0.218

AC:

750

AN:

3452

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.2

DANN

Benign

0.27

Splicing

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