dbSNP rs10578999: TMIE:p.Lys127_Lys131del (chr3-46709583-TAAGAAGAAGAAGAAG-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_147196.3(TMIE):c.379_393delAAGAAGAAGAAGAAG(p.Lys127_Lys131del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TMIE
NM_147196.3 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.54

Publications

21 publications found

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 Gene-Disease associations (from GenCC):

nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive nonsyndromic hearing loss 6
Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TMIE links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
TMIE	NM_147196.3 link	c.379_393delAAGAAGAAGAAGAAG	p.Lys127_Lys131del	conservative_inframe_deletion	Exon 4 of 4	ENST00000643606.3	NP_671729.2
TMIE	NM_001370524.1 link	c.220_234delAAGAAGAAGAAGAAG	p.Lys74_Lys78del	conservative_inframe_deletion	Exon 4 of 4		NP_001357453.1
TMIE	NM_001370525.1 link	c.220_234delAAGAAGAAGAAGAAG	p.Lys74_Lys78del	conservative_inframe_deletion	Exon 5 of 5		NP_001357454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
TMIE	ENST00000643606.3 link	c.379_393delAAGAAGAAGAAGAAG	p.Lys127_Lys131del	conservative_inframe_deletion	Exon 4 of 4	NM_147196.3	ENSP00000494576.2
TMIE	ENST00000644830.1 link	c.220_234delAAGAAGAAGAAGAAG	p.Lys74_Lys78del	conservative_inframe_deletion	Exon 4 of 4		ENSP00000495111.1
TMIE	ENST00000651652.1 link	c.301_315delAAGAAGAAGAAGAAG		3_prime_UTR_variant	Exon 2 of 2		ENSP00000498953.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.13e-7

AC:

AN:

1402592

Hom.:

AF XY:

0.00000143

AC XY:

AN XY:

698904

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31790

American (AMR)

AF:

0.00

AC:

AN:

43630

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25346

East Asian (EAS)

AF:

0.00

AC:

AN:

38820

South Asian (SAS)

AF:

0.00

AC:

AN:

84782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51750

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5628

European-Non Finnish (NFE)

AF:

9.41e-7

AC:

AN:

1062744

Other (OTH)

AF:

0.00

AC:

AN:

58102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

1309

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over