dbSNP rs773120110: TRIM67:p.Gly11Asp (chr1-231163001-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001004342.5(TRIM67):c.32G>A(p.Gly11Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G11A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TRIM67
NM_001004342.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.81

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.822

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM67	NM_001004342.5 link	c.32G>A	p.Gly11Asp	missense_variant	Exon 1 of 10	ENST00000366653.6	NP_001004342.3	Q6ZTA4-3
TRIM67	NM_001410937.1 link	c.32G>A	p.Gly11Asp	missense_variant	Exon 1 of 10		NP_001397866.1
TRIM67	NM_001300889.3 link	c.32G>A	p.Gly11Asp	missense_variant	Exon 1 of 12		NP_001287818.1	Q6ZTA4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRIM67	ENST00000366653.6 link	c.32G>A	p.Gly11Asp	missense_variant	Exon 1 of 10	1	NM_001004342.5	ENSP00000355613.5	Q6ZTA4-3
TRIM67	ENST00000449018.7 link	c.32G>A	p.Gly11Asp	missense_variant	Exon 1 of 12	1		ENSP00000400163.3	Q6ZTA4-2
TRIM67	ENST00000444294.7 link	c.32G>A	p.Gly11Asp	missense_variant	Exon 1 of 10	5		ENSP00000412124.3	F8W8C1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726306

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:

9.00e-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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.;T

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.25

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Uncertain

0.26

MetaRNN

Pathogenic

0.82

D;D;D

MetaSVM

Uncertain

0.045

MutationAssessor

Benign

0.87

.;L;L

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.7

N;N;N

REVEL

Uncertain

0.62

Sift

Uncertain

0.029

D;T;D

Sift4G

Uncertain

0.015

D;T;D

Polyphen

1.0

.;.;D

Vest4

0.71

MutPred

0.34

Gain of ubiquitination at K6 (P = 0.1008);Gain of ubiquitination at K6 (P = 0.1008);Gain of ubiquitination at K6 (P = 0.1008);

MVP

0.87

MPC

1.8

ClinPred

0.86

GERP RS

4.1

Varity_R

0.29

gMVP

0.57

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