Genetic Variant TMIE:p.Gly8Ser (chr3-46701509-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_147196.3(TMIE):c.22G>A(p.Gly8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TMIE
NM_147196.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.01

Publications

0 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: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TMIE links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15000391).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147196.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMIE	NM_147196.3	MANE Select	c.22G>A	p.Gly8Ser	missense	Exon 1 of 4	NP_671729.2	Q8NEW7
TMIE	NM_001370524.1		c.-66-4281G>A		intron	N/A	NP_001357453.1	A0A2R8YDZ8
TMIE	NM_001370525.1		c.-66-4281G>A		intron	N/A	NP_001357454.1	A0A2R8YDZ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMIE	ENST00000643606.3	MANE Select	c.22G>A	p.Gly8Ser	missense	Exon 1 of 4	ENSP00000494576.2	Q8NEW7
	TMIE	ENST00000644830.1		c.-66-4281G>A		intron	N/A	ENSP00000495111.1	A0A2R8YDZ8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1189618

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

574522

African (AFR)

AF:

0.00

AC:

AN:

23756

American (AMR)

AF:

0.00

AC:

AN:

9482

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16526

East Asian (EAS)

AF:

0.00

AC:

AN:

26960

South Asian (SAS)

AF:

0.00

AC:

AN:

48032

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4512

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

983130

Other (OTH)

AF:

0.00

AC:

AN:

48776

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.072

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.51

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.56

MutationAssessor

Benign

0.55

PhyloP100

2.0

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.24

REVEL

Benign

0.098

Sift

Benign

0.044

Sift4G

Benign

0.54

Polyphen

0.025

Vest4

0.29

MutPred

0.38

Gain of glycosylation at G8 (P = 0.0296)

MVP

0.49

MPC

0.28

ClinPred

0.16

GERP RS

2.2

PromoterAI

0.061

Neutral

(source)

Varity_R

0.054

gMVP

0.56

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over