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

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_147196.3(TMIE):c.382_393del(p.Lys128_Lys131del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,552,536 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

TMIE
NM_147196.3 inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.54

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 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

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMIE	NM_147196.3 linkuse as main transcript	c.382_393del	p.Lys128_Lys131del	inframe_deletion	4/4	ENST00000643606.3	NP_671729.2
TMIE	NM_001370524.1 linkuse as main transcript	c.223_234del	p.Lys75_Lys78del	inframe_deletion	4/4		NP_001357453.1
TMIE	NM_001370525.1 linkuse as main transcript	c.223_234del	p.Lys75_Lys78del	inframe_deletion	5/5		NP_001357454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	Appris
TMIE	ENST00000643606.3 linkuse as main transcript	c.382_393del	p.Lys128_Lys131del	inframe_deletion	4/4	NM_147196.3	ENSP00000494576	P1
TMIE	ENST00000644830.1 linkuse as main transcript	c.223_234del	p.Lys75_Lys78del	inframe_deletion	4/4		ENSP00000495111
TMIE	ENST00000651652.1 linkuse as main transcript	c.304_315del		3_prime_UTR_variant	2/2		ENSP00000498953

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

149948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000114

AC:

AN:

1402588

Hom.:

AF XY:

0.00000858

AC XY:

AN XY:

698902

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000258

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000141

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000133

AC:

AN:

149948

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73004

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000296

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over