Variant chr3-46701033-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001370524.1(TMIE):c.-66-4757C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0959 in 147,950 control chromosomes in the GnomAD database, including 783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.096 ( 783 hom., cov: 30)

Consequence

TMIE
NM_001370524.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.439

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 3-46701033-C-A is Benign according to our data. Variant chr3-46701033-C-A is described in ClinVar as [Benign]. Clinvar id is 1258770.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMIE	NM_001370524.1 linkuse as main transcript	c.-66-4757C>A		intron_variant
TMIE	NM_001370525.1 linkuse as main transcript	c.-66-4757C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMIE	ENST00000644830.1 linkuse as main transcript	c.-66-4757C>A		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0957

AC:

14148

AN:

147838

Hom.:

778

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.00442

Gnomad AMR

AF:

0.0894

Gnomad ASJ

AF:

0.0882

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.0518

Gnomad MID

AF:

0.128

Gnomad NFE

AF:

0.0697

Gnomad OTH

AF:

0.0967

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0959

AC:

14192

AN:

147950

Hom.:

783

Cov.:

AF XY:

0.0957

AC XY:

6911

AN XY:

72234

show subpopulations

Gnomad4 AFR

AF:

0.153

Gnomad4 AMR

AF:

0.0893

Gnomad4 ASJ

AF:

0.0882

Gnomad4 EAS

AF:

0.129

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.0518

Gnomad4 NFE

AF:

0.0698

Gnomad4 OTH

AF:

0.0963

Alfa

AF:

0.0293

Hom.:

Bravo

AF:

0.0982

Asia WGS

AF:

0.130

AC:

453

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.4

DANN

Benign

0.79

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