Variant 3-46709583-TAAGAAGAAGAAGAAG-TAAGAAGAAGAAGAAGAAGAAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM1BP6_Very_StrongBS1

The NM_147196.3(TMIE):c.388_393dup(p.Lys130_Lys131dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

TMIE
NM_147196.3 inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.773

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 -10 ACMG points.

PM1

In a chain Transmembrane inner ear expressed protein (size 128) in uniprot entity TMIE_HUMAN there are 6 pathogenic changes around while only 2 benign (75%) in NM_147196.3

BP6

Variant 3-46709583-T-TAAGAAG is Benign according to our data. Variant chr3-46709583-T-TAAGAAG is described in ClinVar as [Likely_benign]. Clinvar id is 515000.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 = 0.000793 (119/150058) while in subpopulation AFR AF= 0.0027 (110/40804). AF 95% confidence interval is 0.00229. There are 0 homozygotes in gnomad4. There are 59 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMIE	NM_147196.3 linkuse as main transcript	c.388_393dup	p.Lys130_Lys131dup	inframe_insertion	4/4	ENST00000643606.3	NP_671729.2
TMIE	NM_001370524.1 linkuse as main transcript	c.229_234dup	p.Lys77_Lys78dup	inframe_insertion	4/4		NP_001357453.1
TMIE	NM_001370525.1 linkuse as main transcript	c.229_234dup	p.Lys77_Lys78dup	inframe_insertion	5/5		NP_001357454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	Appris
TMIE	ENST00000643606.3 linkuse as main transcript	c.388_393dup	p.Lys130_Lys131dup	inframe_insertion	4/4	NM_147196.3	ENSP00000494576	P1
TMIE	ENST00000644830.1 linkuse as main transcript	c.229_234dup	p.Lys77_Lys78dup	inframe_insertion	4/4		ENSP00000495111
TMIE	ENST00000651652.1 linkuse as main transcript	c.310_315dup		3_prime_UTR_variant	2/2		ENSP00000498953

Frequencies

GnomAD3 genomes

AF:

0.000780

AC:

117

AN:

149948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000465

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.000484

GnomAD3 exomes

AF:

0.000405

AC:

AN:

145554

Hom.:

AF XY:

0.000447

AC XY:

AN XY:

78324

show subpopulations

Gnomad AFR exome

AF:

0.00577

Gnomad AMR exome

AF:

0.000200

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000889

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000559

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000123

AC:

173

AN:

1402588

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

698900

show subpopulations

Gnomad4 AFR exome

AF:

0.00349

Gnomad4 AMR exome

AF:

0.0000917

Gnomad4 ASJ exome

AF:

0.0000395

Gnomad4 EAS exome

AF:

0.0000258

Gnomad4 SAS exome

AF:

0.0000236

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000395

Gnomad4 OTH exome

AF:

0.000207

GnomAD4 genome

AF:

0.000793

AC:

119

AN:

150058

Hom.:

Cov.:

AF XY:

0.000807

AC XY:

AN XY:

73126

show subpopulations

Gnomad4 AFR

AF:

0.00270

Gnomad4 AMR

AF:

0.000465

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.000478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 25, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 10, 2023	- -

TMIE-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 29, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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