Variant 1-231163501-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 NM_001004342.5(TRIM67):c.532C>A(p.Arg178Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000439 in 1,367,106 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R178L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

TRIM67
NM_001004342.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.682

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	UniProt
TRIM67	NM_001004342.5 linkuse as main transcript	c.532C>A	p.Arg178Ser	missense_variant	1/10	ENST00000366653.6	NP_001004342.3	Q6ZTA4-3
TRIM67	NM_001410937.1 linkuse as main transcript	c.532C>A	p.Arg178Ser	missense_variant	1/10		NP_001397866.1
TRIM67	NM_001300889.3 linkuse as main transcript	c.412C>A	p.Arg138Ser	missense_variant	2/12		NP_001287818.1	Q6ZTA4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRIM67	ENST00000366653.6 linkuse as main transcript	c.532C>A	p.Arg178Ser	missense_variant	1/10	1	NM_001004342.5	ENSP00000355613.5	Q6ZTA4-3
TRIM67	ENST00000449018.7 linkuse as main transcript	c.412C>A	p.Arg138Ser	missense_variant	2/12	1		ENSP00000400163.3	Q6ZTA4-2
TRIM67	ENST00000444294.7 linkuse as main transcript	c.532C>A	p.Arg178Ser	missense_variant	1/10	5		ENSP00000412124.3	F8W8C1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000268

AC:

AN:

112050

Hom.:

AF XY:

0.0000322

AC XY:

AN XY:

62200

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000138

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000101

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000439

AC:

AN:

1367106

Hom.:

Cov.:

AF XY:

0.00000445

AC XY:

AN XY:

674542

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000411

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000521

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.33e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000201

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

Jul 15, 2021

The c.532C>A (p.R178S) 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 532, causing the arginine (R) at amino acid position 178 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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.078

T;.;T

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Pathogenic

0.83

MetaRNN

Uncertain

0.49

T;T;T

MetaSVM

Uncertain

-0.055

MutationAssessor

Uncertain

2.3

.;.;M

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-2.5

D;N;N

REVEL

Uncertain

0.57

Sift

Uncertain

0.015

D;D;D

Sift4G

Uncertain

0.040

D;D;D

Polyphen

0.96

.;.;P

Vest4

0.49

MutPred

0.56

Loss of MoRF binding (P = 0.0483);.;Loss of MoRF binding (P = 0.0483);

MVP

0.66

MPC

1.6

ClinPred

0.65

GERP RS

4.2

Varity_R

0.53

gMVP

0.79

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