rs765221463
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_147196.3(TMIE):c.123G>A(p.Pro41=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,614,028 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000079 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
TMIE
NM_147196.3 synonymous
NM_147196.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0840
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
?
Variant 3-46705819-G-A is Benign according to our data. Variant chr3-46705819-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 517406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.084 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMIE | NM_147196.3 | c.123G>A | p.Pro41= | synonymous_variant | 2/4 | ENST00000643606.3 | |
TMIE | NM_001370524.1 | c.-37G>A | 5_prime_UTR_variant | 2/4 | |||
TMIE | NM_001370525.1 | c.-37G>A | 5_prime_UTR_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMIE | ENST00000643606.3 | c.123G>A | p.Pro41= | synonymous_variant | 2/4 | NM_147196.3 | P1 | ||
TMIE | ENST00000651652.1 | c.21G>A | p.Pro7= | synonymous_variant | 1/2 | ||||
TMIE | ENST00000644830.1 | c.-37G>A | 5_prime_UTR_variant | 2/4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152164Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000124 AC: 31AN: 249478Hom.: 0 AF XY: 0.000148 AC XY: 20AN XY: 135388
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GnomAD4 exome AF: 0.000135 AC: 197AN: 1461746Hom.: 0 Cov.: 32 AF XY: 0.000147 AC XY: 107AN XY: 727182
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GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152282Hom.: 1 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74456
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 31, 2017 | p.Pro41Pro in exon 2 of TMIE: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 20/126670 European c hromosomes and 7/30782 South Asian chromosomes by the Genome Aggregation Databas e (gnomAD, http://gnomad.broadinstitute.org/; dbSNP rs765221463). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 28, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at