Variant 1-231163105-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000366653.6(TRIM67):c.136C>T(p.Pro46Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000153 in 1,567,788 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

TRIM67
ENST00000366653.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060989976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRIM67	NM_001004342.5 linkuse as main transcript	c.136C>T	p.Pro46Ser	missense_variant	1/10	ENST00000366653.6	NP_001004342.3
TRIM67	NM_001410937.1 linkuse as main transcript	c.136C>T	p.Pro46Ser	missense_variant	1/10		NP_001397866.1
TRIM67	NM_001300889.3 linkuse as main transcript	c.121+15C>T		intron_variant			NP_001287818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM67	ENST00000366653.6 linkuse as main transcript	c.136C>T	p.Pro46Ser	missense_variant	1/10	1	NM_001004342.5	ENSP00000355613	A1	Q6ZTA4-3
TRIM67	ENST00000449018.7 linkuse as main transcript	c.121+15C>T		intron_variant		1		ENSP00000400163		Q6ZTA4-2
TRIM67	ENST00000444294.7 linkuse as main transcript	c.136C>T	p.Pro46Ser	missense_variant	1/10	5		ENSP00000412124	P3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000573

AC:

AN:

174664

Hom.:

AF XY:

0.0000105

AC XY:

AN XY:

94874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000136

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000162

AC:

AN:

1415552

Hom.:

Cov.:

AF XY:

0.0000186

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:

0.0000211

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000317

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000853

AC:

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

Jun 16, 2024

The c.136C>T (p.P46S) alteration is located in exon 1 (coding exon 1) of the TRIM67 gene. This alteration results from a C to T substitution at nucleotide position 136, causing the proline (P) at amino acid position 46 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

T;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.56

T;T

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;L

MutationTaster

Benign

0.98

D;D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.65

N;N

REVEL

Benign

0.11

Sift

Benign

0.33

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.0080

.;B

Vest4

0.034

MutPred

0.20

Loss of loop (P = 0.0986);Loss of loop (P = 0.0986);

MVP

0.25

MPC

0.73

ClinPred

0.098

GERP RS

3.9

Varity_R

0.063

gMVP

0.45

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over