rs777735001

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004342.5(TRIM67):​c.136C>A​(p.Pro46Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,415,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P46S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

TRIM67
NM_001004342.5 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.198
Variant links:
Genes affected
TRIM67 (HGNC:31859): (tripartite motif containing 67) Predicted to enable zinc ion binding activity. Predicted to be involved in regulation of protein localization. Predicted to act upstream of or within negative regulation of Ras protein signal transduction; positive regulation of neuron projection development; and positive regulation of ubiquitin-dependent protein catabolic process. Predicted to be located in cytoplasm and cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09568328).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM67NM_001004342.5 linkc.136C>A p.Pro46Thr missense_variant Exon 1 of 10 ENST00000366653.6 NP_001004342.3 Q6ZTA4-3
TRIM67NM_001410937.1 linkc.136C>A p.Pro46Thr missense_variant Exon 1 of 10 NP_001397866.1
TRIM67NM_001300889.3 linkc.121+15C>A intron_variant Intron 1 of 11 NP_001287818.1 Q6ZTA4-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM67ENST00000366653.6 linkc.136C>A p.Pro46Thr missense_variant Exon 1 of 10 1 NM_001004342.5 ENSP00000355613.5 Q6ZTA4-3
TRIM67ENST00000449018.7 linkc.121+15C>A intron_variant Intron 1 of 11 1 ENSP00000400163.3 Q6ZTA4-2
TRIM67ENST00000444294.7 linkc.136C>A p.Pro46Thr missense_variant Exon 1 of 10 5 ENSP00000412124.3 F8W8C1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.06e-7
AC:
1
AN:
1415552
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
700776
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.17e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.060
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.025
T;T
Eigen
Benign
-0.40
Eigen_PC
Benign
-0.21
FATHMM_MKL
Benign
0.53
D
LIST_S2
Benign
0.54
T;T
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.096
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
.;L
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-1.3
N;N
REVEL
Benign
0.12
Sift
Benign
0.031
D;D
Sift4G
Benign
0.21
T;T
Polyphen
0.067
.;B
Vest4
0.044
MutPred
0.29
Gain of glycosylation at P46 (P = 0.0656);Gain of glycosylation at P46 (P = 0.0656);
MVP
0.32
MPC
1.3
ClinPred
0.47
T
GERP RS
3.9
Varity_R
0.12
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-231298851; API