dbSNP rs777735001: TRIM67:p.Pro46Thr (chr1-231163105-C-A) – ACMG Classification: Uncertain_significance (0 pts)

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

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]

TRIM67 links:

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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
TRIM67	NM_001004342.5 link	c.136C>A	p.Pro46Thr	missense_variant	Exon 1 of 10	ENST00000366653.6	NP_001004342.3	Q6ZTA4-3
TRIM67	NM_001410937.1 link	c.136C>A	p.Pro46Thr	missense_variant	Exon 1 of 10		NP_001397866.1
TRIM67	NM_001300889.3 link	c.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	UniProt
TRIM67	ENST00000366653.6 link	c.136C>A	p.Pro46Thr	missense_variant	Exon 1 of 10	1	NM_001004342.5	ENSP00000355613.5	Q6ZTA4-3
TRIM67	ENST00000449018.7 link	c.121+15C>A		intron_variant	Intron 1 of 11	1		ENSP00000400163.3	Q6ZTA4-2
TRIM67	ENST00000444294.7 link	c.136C>A	p.Pro46Thr	missense_variant	Exon 1 of 10	5		ENSP00000412124.3	F8W8C1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.06e-7

AC:

AN:

1415552

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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.:

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

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

T;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.54

T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.096

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

.;L

PrimateAI

Uncertain

0.78

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over