Variant 1-231163717-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000366653.6(TRIM67):c.748C>A(p.Leu250Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIM67
ENST00000366653.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.695

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRIM67	NM_001004342.5 linkuse as main transcript	c.748C>A	p.Leu250Met	missense_variant	1/10	ENST00000366653.6	NP_001004342.3
TRIM67	NM_001410937.1 linkuse as main transcript	c.748C>A	p.Leu250Met	missense_variant	1/10		NP_001397866.1
TRIM67	NM_001300889.3 linkuse as main transcript	c.628C>A	p.Leu210Met	missense_variant, splice_region_variant	2/12		NP_001287818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM67	ENST00000366653.6 linkuse as main transcript	c.748C>A	p.Leu250Met	missense_variant	1/10	1	NM_001004342.5	ENSP00000355613	A1	Q6ZTA4-3
TRIM67	ENST00000449018.7 linkuse as main transcript	c.628C>A	p.Leu210Met	missense_variant, splice_region_variant	2/12	1		ENSP00000400163		Q6ZTA4-2
TRIM67	ENST00000444294.7 linkuse as main transcript	c.748C>A	p.Leu250Met	missense_variant	1/10	5		ENSP00000412124	P3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1350324

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

665732

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jul 08, 2022

The c.748C>A (p.L250M) alteration is located in exon 1 (coding exon 1) of the TRIM67 gene. This alteration results from a C to A substitution at nucleotide position 748, causing the leucine (L) at amino acid position 250 to be replaced by a methionine (M). 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

Pathogenic

0.60

BayesDel_addAF

Uncertain

0.039

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;.;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.65

T;T;T

M_CAP

Pathogenic

0.86

MetaRNN

Uncertain

0.44

T;T;T

MetaSVM

Benign

-0.35

MutationAssessor

Benign

0.81

.;.;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.5

N;N;N

REVEL

Uncertain

0.45

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0070

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.35

MutPred

0.24

Gain of methylation at K247 (P = 0.0872);.;Gain of methylation at K247 (P = 0.0872);

MVP

0.76

MPC

1.5

ClinPred

0.82

GERP RS

2.4

Varity_R

0.50

gMVP

0.43

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