12-108592272-C-T
Position:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_181724.3(TMEM119):c.112G>A(p.Val38Met) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 31)
Consequence
TMEM119
NM_181724.3 missense
NM_181724.3 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: -2.01
Genes affected
TMEM119 (HGNC:27884): (transmembrane protein 119) Involved in positive regulation of bone mineralization; positive regulation of osteoblast differentiation; and positive regulation of osteoblast proliferation. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.034668475).
BP6
Variant 12-108592272-C-T is Benign according to our data. Variant chr12-108592272-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2481103.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| TMEM119 | ENST00000392806.4 | c.112G>A | p.Val38Met | missense_variant | 2/2 | 1 | NM_181724.3 | ENSP00000376553.3 | ||
| TMEM119 | ENST00000549031.1 | c.112G>A | p.Val38Met | missense_variant | 3/3 | 4 | ENSP00000448583.1 | |||
| TMEM119 | ENST00000549447.1 | c.112G>A | p.Val38Met | missense_variant | 3/3 | 4 | ENSP00000447120.1 | |||
| TMEM119 | ENST00000547567.1 | c.*28G>A | downstream_gene_variant | 2 | ENSP00000447345.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 35
GnomAD4 exome
Cov.:
35
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 06, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;.
Sift4G
Uncertain
T;.;T
Polyphen
B;.;.
Vest4
MutPred
Gain of catalytic residue at A39 (P = 0.0147);Gain of catalytic residue at A39 (P = 0.0147);Gain of catalytic residue at A39 (P = 0.0147);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.