Variant 17-75875097-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_033452.3(TRIM47):c.1303G>A(p.Asp435Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,603,438 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TRIM47
NM_033452.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.50

Variant links:

Genes affected

TRIM47 (HGNC:19020): (tripartite motif containing 47) Enables ubiquitin-protein transferase activity. Involved in protein ubiquitination. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TRIM47 links:

TRIM47 (HGNC:):

TRIM47 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=0.15157136).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM47	NM_033452.3 linkuse as main transcript	c.1303G>A	p.Asp435Asn	missense_variant	6/6	ENST00000254816.6	NP_258411.2	Q96LD4-1
TRIM47	XM_005257787.5 linkuse as main transcript	c.589G>A	p.Asp197Asn	missense_variant	6/6		XP_005257844.1	Q96LD4-2
TRIM47	XM_005257788.6 linkuse as main transcript	c.589G>A	p.Asp197Asn	missense_variant	6/6		XP_005257845.1	Q96LD4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRIM47	ENST00000254816.6 linkuse as main transcript	c.1303G>A	p.Asp435Asn	missense_variant	6/6	1	NM_033452.3	ENSP00000254816.1	Q96LD4-1
TRIM47	ENST00000587339.2 linkuse as main transcript	n.*606G>A		non_coding_transcript_exon_variant	6/6	1		ENSP00000465010.2	A0A0M3HER3
TRIM47	ENST00000587339.2 linkuse as main transcript	n.*606G>A		3_prime_UTR_variant	6/6	1		ENSP00000465010.2	A0A0M3HER3
TRIM47	ENST00000592942.1 linkuse as main transcript	n.219G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152134

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000529

AC:

AN:

245930

Hom.:

AF XY:

0.0000300

AC XY:

AN XY:

133166

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000350

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000337

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000145

AC:

AN:

1451304

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

720054

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.000248

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000543

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74310

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000165

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

Mar 24, 2023

The c.1303G>A (p.D435N) alteration is located in exon 6 (coding exon 6) of the TRIM47 gene. This alteration results from a G to A substitution at nucleotide position 1303, causing the aspartic acid (D) at amino acid position 435 to be replaced by an asparagine (N). 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

0.28

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.017

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.070

FATHMM_MKL

Benign

0.57

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.013

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.22

PrimateAI

Uncertain

0.70

PROVEAN

Benign

1.4

REVEL

Benign

0.19

Sift

Benign

0.51

Sift4G

Pathogenic

0.0

Polyphen

0.68

Vest4

0.29

MutPred

0.40

Loss of stability (P = 0.0654);

MVP

0.61

MPC

0.68

ClinPred

0.15

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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