1-155181869-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_025058.5(TRIM46):c.1606G>A(p.Asp536Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000683 in 1,611,070 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000069 ( 0 hom. )
Consequence
TRIM46
NM_025058.5 missense
NM_025058.5 missense
Scores
3
9
6
Clinical Significance
Conservation
PhyloP100: 9.29
Genes affected
TRIM46 (HGNC:19019): (tripartite motif containing 46) This gene encodes a protein of the tripartite motif (TRIM) family. The TRIM motif includes zinc-binding domains, a RING finger region, a B-box motif and a coiled-coil domain. TRIM46 is reported to be involved in the proliferation of multiple types of cancer cells including lung and breast cancer. It has also been shown to control neuronal polarity and axon specification by forming uniform microtubule bundles in the axon. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, TRIM46
BS2
?
High AC in GnomAdExome at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRIM46 | NM_025058.5 | c.1606G>A | p.Asp536Asn | missense_variant | 9/10 | ENST00000334634.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIM46 | ENST00000334634.9 | c.1606G>A | p.Asp536Asn | missense_variant | 9/10 | 1 | NM_025058.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000203 AC: 5AN: 246360Hom.: 0 AF XY: 0.0000299 AC XY: 4AN XY: 133878
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GnomAD4 exome AF: 0.00000685 AC: 10AN: 1458870Hom.: 0 Cov.: 32 AF XY: 0.00000689 AC XY: 5AN XY: 725222
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3478
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 | Feb 27, 2024 | The c.1606G>A (p.D536N) alteration is located in exon 9 (coding exon 9) of the TRIM46 gene. This alteration results from a G to A substitution at nucleotide position 1606, causing the aspartic acid (D) at amino acid position 536 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;.;T;.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D;D;D;.
REVEL
Uncertain
Sift
Uncertain
D;.;D;D;D;.
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
1.0
.;.;D;.;D;.
Vest4
MutPred
0.50
.;.;Gain of MoRF binding (P = 0.0389);.;Gain of MoRF binding (P = 0.0389);.;
MVP
MPC
1.7
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 5
Find out detailed SpliceAI scores and Pangolin per-transcript scores at