12-66153364-G-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000544599.5(TMBIM4):c.-350C>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TMBIM4
ENST00000544599.5 5_prime_UTR_premature_start_codon_gain
ENST00000544599.5 5_prime_UTR_premature_start_codon_gain
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 3.25
Genes affected
TMBIM4 (HGNC:24257): (transmembrane BAX inhibitor motif containing 4) Involved in negative regulation of apoptotic process and regulation of calcium-mediated signaling. Located in Golgi stack. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMBIM4 | NM_016056.4 | c.182C>A | p.Ser61Tyr | missense_variant | 2/7 | ENST00000358230.8 | NP_057140.2 | |
TMBIM4 | NM_001282606.2 | c.323C>A | p.Ser108Tyr | missense_variant | 3/8 | NP_001269535.1 | ||
TMBIM4 | NM_001282610.2 | c.89C>A | p.Ser30Tyr | missense_variant | 2/7 | NP_001269539.1 | ||
TMBIM4 | NM_001282609.2 | c.182C>A | p.Ser61Tyr | missense_variant | 2/7 | NP_001269538.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMBIM4 | ENST00000358230.8 | c.182C>A | p.Ser61Tyr | missense_variant | 2/7 | 1 | NM_016056.4 | ENSP00000350965.3 | ||
ENSG00000228144 | ENST00000539652.1 | n.182C>A | non_coding_transcript_exon_variant | 2/8 | 2 | ENSP00000454670.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1437832Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0AN XY: 715972
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1437832
Hom.:
Cov.:
27
AF XY:
AC XY:
0
AN XY:
715972
Gnomad4 AFR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 07, 2024 | The c.182C>A (p.S61Y) alteration is located in exon 2 (coding exon 2) of the TMBIM4 gene. This alteration results from a C to A substitution at nucleotide position 182, causing the serine (S) at amino acid position 61 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.;.;.
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.;D;D;.;D
REVEL
Benign
Sift
Benign
D;.;D;D;.;D
Sift4G
Uncertain
D;D;T;D;T;T
Polyphen
P;.;D;D;.;.
Vest4
MutPred
0.56
.;.;.;Gain of helix (P = 0.132);.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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