Variant chr16-31215123-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001008274.4(TRIM72):c.385C>T(p.Leu129Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,440,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

TRIM72
NM_001008274.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96

Variant links:

Genes affected

TRIM72 (HGNC:32671): (tripartite motif containing 72) Enables identical protein binding activity. Predicted to be involved in several processes, including cellular protein metabolic process; plasma membrane repair; and protein homooligomerization. Predicted to act upstream of or within negative regulation of insulin receptor signaling pathway; negative regulation of insulin-like growth factor receptor signaling pathway; and negative regulation of myotube differentiation. Predicted to be located in cytoplasmic vesicle membrane. Predicted to be active in cytoplasm and sarcolemma. [provided by Alliance of Genome Resources, Apr 2022]

TRIM72 links:

Genome browser will be placed here

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=0.07578817).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM72	NM_001008274.4 linkuse as main transcript	c.385C>T	p.Leu129Phe	missense_variant	2/7	ENST00000322122.8	NP_001008275.2	Q6ZMU5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM72	ENST00000322122.8 linkuse as main transcript	c.385C>T	p.Leu129Phe	missense_variant	2/7	2	NM_001008274.4	ENSP00000312675.3		Q6ZMU5-1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000142

AC:

AN:

98822

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

56066

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000334

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:

0.000167

Gnomad OTH exome

AF:

0.000528

GnomAD4 exome

AF:

0.000117

AC:

151

AN:

1288466

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

628724

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000571

Gnomad4 ASJ exome

AF:

0.000928

Gnomad4 EAS exome

AF:

0.0000315

Gnomad4 SAS exome

AF:

0.000222

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000838

Gnomad4 OTH exome

AF:

0.000151

GnomAD4 genome

AF:

0.000190

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.0000489

Hom.:

Bravo

AF:

0.000268

ExAC

AF:

0.000126

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

Dec 21, 2022

The c.385C>T (p.L129F) alteration is located in exon 2 (coding exon 1) of the TRIM72 gene. This alteration results from a C to T substitution at nucleotide position 385, causing the leucine (L) at amino acid position 129 to be replaced by a phenylalanine (F). 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

0.31

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.050

T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.059

MetaRNN

Benign

0.076

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

0.86

PrimateAI

Uncertain

0.71

PROVEAN

Benign

0.45

N;.

REVEL

Benign

0.061

Sift

Benign

0.040

D;.

Sift4G

Benign

0.16

T;T

Polyphen

0.81

P;.

Vest4

0.17

MutPred

0.41

Gain of methylation at K130 (P = 0.025);Gain of methylation at K130 (P = 0.025);

MVP

0.70

ClinPred

0.039

GERP RS

2.7

Varity_R

0.11

gMVP

0.19

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